Admission serum high mobility group box 1 (HMGB1) protein predicts delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

High mobility group box 1 protein (HMGB1) is a prototypical damage associated particle and acts as a key player in aseptic inflammation. HMGB1 appears critical for the crosstalk of a prothrombotic and proinflammatory state that is implicated in mediating and exacerbating ischemic brain injury. The role of HMGB1 in aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated. A prospective, single blinded observational study was designed to investigate the role of HMGB1 in aSAH. Serial serum HMGB1 level quantification on admission day 0, 4, 8, and 12 was performed. Primary outcome measures were delayed cerebral ischemia (DCI - new infarction on CT) and poor functional outcome (90-day modified Rankin Scale 4-6). The role of HMGB1 levels for DCI, functional outcome and radiological vasospasm prediction was analyzed. Collectively, 83 aSAH patients were enrolled. Five patients died within 48 h. In 29/78 patients (37.2%), DCI was identified. In multivariable analysis, radiological vasospasm and admission HMGB1 were independent predictors for DCI. Younger age and higher white blood cell count, but not insult burden (World Federation of Neurosurgical Societies scale, modified Fisher scale, intraparenchymal or intraventricular hematoma existence) correlated with admission HMGB1 levels. Serial HMGB1 levels did not differ between patients with or without DCI, poor functional outcome or radiological vasospasm development. Admission serum HMGB1 does not reflect initial insult burden but serves as an independent biomarker predictive of DCI. Further studies are warranted to disentangle the role of HMGB1 surrounding the sequelae of aSAH.

Management of severe intraoperative hemorrhage during intraventricular neuroendoscopic procedures: the dry field technique.

OBJECTIVE: Neuroendoscopic procedures inside the ventricular system always bear the risk for an unexpected intraoperative hemorrhage with potentially devastating consequences. The authors present here their experience, and a stage-to-stage guide for the endoscopic management of intraoperative hemorrhages. METHODS: A step-by-step guide for the management to gain control of and stop the bleeding is described including a grading system. More advanced techniques are presented in cases examples. CONCLUSION: Most of intraoperative hemorrhages can be controlled by constant irrigation and coagulation. More advanced techniques can be applied quickly and easily to ensure control of the hemorrhages and avoid the need for a microsurgical conversion.

The extended endoscopic approach to perisellar and skull base lesions: is one nostril enough?

The extended endonasal endoscopic approach to the skull base is still under investigation. The main advantage of using this technique is to approach lesions in a minimally invasive manner resulting without brain retraction. Here, the authors present the results of extended endonasal endoscopic surgery via one nostril. All skull base procedures performed via an endonasal approach at the author's Department between January 2011 and May 2017 were analysed prospectively. Special attention was paid to complications, radicality, advantages and disadvantages of the endoscopic technique. Additionally, the application of various telescopes and the technique of dural closure were analysed. Sixty-two patients were operated on various pathologies of the skull base via an extended endonasal approach. Seven pathologies were resected via binostril technique. All other pathologies could be exposed by the mononostril technique. In 2 of 62 cases, the authors had to switch to binostril technique. MRI revealed radical gross total resection in 93% of all cases when intended. Overall complication rate was 16% (9/55) in the mononostril and 57% (4/7) in the binostril cohort. Seven patients in the mononostril cohort (13%) versus three patients in the binostril cohort (43%) complained of postoperative nasal congestion. This clinical report shows that many extended skull base lesions can be treated by a mononostril endonasal approach. In selected cases, this technique might represent an alternative to the binostril approach. Nevertheless, the binostril technique offers a better range of manipulation and exposure and should be preferred in difficult and very extended cases.

Loss of consciousness at onset of aneurysmal subarachnoid hemorrhage in good-grade patients.

Loss of consciousness (LOC) at presentation with aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury and poor functional outcome. The impact of LOC on the clinical course after aSAH deserves further exploration. A retrospective analysis of 149 aSAH patients who were prospectively enrolled in the Cerebral Aneurysm Renin Angiotensin Study (CARAS) between 2012 and 2015 was performed. The impact of LOC was analyzed with emphasis on patients presenting in excellent or good neurological condition (Hunt and Hess 1 and 2). A total of 50/149 aSAH patients (33.6%) experienced LOC at presentation. Loss of consciousness was associated with severity of neurological condition upon admission (Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), Glasgow Coma Scale (GCS) grade), hemorrhage burden on initial head CT (Fisher CT grade), acute hydrocephalus, cardiac instability, and nosocomial infection. Of Hunt and Hess grade 1 and 2 patients, 21/84 (25.0%) suffered LOC at presentation. Cardiac instability and nosocomial infection were significantly more frequent in these patients. In multivariable analysis, LOC was the predominant predictor of cardiac instability and nosocomial infection. Loss of consciousness at presentation with aSAH is associated with an increased rate of complications, even in good-grade patients. The presence of LOC may identify good-grade patients at risk for complications such as cardiac instability and nosocomial infection.

Intra-catheter endoscopy for various shunting procedures-a retrospective analysis on surgical practicability, catheter placement, and failure rates.

BACKGROUND: The long-term function of a cerebral shunt is directly influenced by the placement of the ventricle catheter. In this work, an intra-luminal endoscope for best possible catheter positioning was used. Practicability, postoperative imaging, and shunt failure rates were retrospectively evaluated. METHODS: Between January 2012 and June 2016, an intra-catheter endoscope was applied in 71 procedures. Endoscopic technique was used for catheter placement in first-time shunting or cerebrospinal fluid reservoir insertion (n = 38), revision surgery in proximal shunt failure (n = 13), and various intraventricular stenting procedures (n = 20). Catheter positioning was graded on postoperative imaging using a four-point scale. All patients were regularly followed up (mean, 31.6 months) to recognize shunt failures. RESULTS: Endoscopic application could be completed as intended in 68 of 71 procedures. Postoperative imaging could exclude complete misplacement of all catheters, but optimal positioning was only achieved in 64.7% (44/68 cases). Four catheters had to be revised due to malfunction (failure rate, 5.8%). Another five catheters had to be removed due to infectious complications or wound-healing disorders. Direct correlations between catheter complications and suboptimal catheter positioning were not seen. Slit or distorted ventricles also did not prove to be a risk factor for the observed complications. CONCLUSIONS: Versatile application possibilities of the intra-catheter endoscope reflect the advantages of the technique. Independent of the performed procedure, unintended positionings or even complete catheter misplacements could be avoided. However, in more than one-third of all cases, suboptimal catheter placements became obvious. Interestingly, negative influences on later shunt failures were not seen.

Darbepoetin-α Promotes Cell Proliferation in Established Extrahepatic Colorectal Tumors after Major Hepatectomy.

BACKGROUND: The glycoprotein hormone erythropoietin and its analogue darbepoetin-α (DPO) have been shown to reduce the risk of acute liver failure after major hepatectomy. However, previous experimental studies have also shown that DPO significantly enhances neovascularization and tumor cell proliferation in established colorectal liver metastasis in hepatectomized and nonhepatectomized mice. The present study now analyzes whether DPO influences cell proliferation and migration as well as vascularization and growth of established colorectal metastasis at extrahepatic sites after major hepatectomy. METHODS: GFP-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Five days after tumor cell implantation, the animals received a single dose of DPO (10 µg/kg body weight) or phosphate-buffered saline solution (PBS) intravenously. Additional animals received a 70% hepatectomy and DPO or PBS treatment. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied repetitively over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry. RESULTS: DPO did not influence tumor cell migration and apoptosis. In addition, DPO did not stimulate tumor cell infiltration or vascularization; however, significantly increased tumor cell proliferation was detected in hepatectomized animals. CONCLUSION: DPO increases cell proliferation in established extrahepatic colorectal metastases after major hepatectomy. Thus, DPO may not be recommended to stimulate regeneration of the remnant liver after major hepatectomy for colorectal liver metastasis.

Preoperative navigated transcranial magnetic stimulation in patients with motor eloquent lesions with emphasis on metastasis.

Navigated transcranial magnetic stimulation (nTMS) is a frequently used, non-invasive method to map the motor cortex. It is of great value in the preoperative workup of patients that suffer from motor eloquent brain lesions. Here, we present a single-center experience using preoperative nTMS in cortical motor eloquent lesions with emphasis on metastasis. All patients that underwent preoperative nTMS between June 2013 and January 2016 were evaluated. A total of 61 patients underwent nTMS before undergoing surgery for a motor eloquent brain lesion. Patients suffered from cerebral metastasis (23), glioblastoma (16), high grade glioma WHO III (4), low grade glioma WHO II (4), lymphoma (2), meningioma (8), cavernous hemangioma (3), or arteriovenous malformation (1). Thirty patients (49.2%) presented with a preoperative motor deficit. One week after surgery, paresis had resolved or improved in 56.7% of the patients. Out of the patients with postoperative paresis, 89.5% experienced an improvement of motor status at follow-up. All metastatic lesions were completely resected compared to 78.9% of non-metastatic lesions (P = 0.02). Only 4.3% of patients with a metastatic lesion, but 26.3% of patients with a non-metastatic lesion experienced deterioration of motor function after surgery (P = 0.04). Preoperative nTMS is suitable for mapping of a variety of motor eloquent brain lesions resulting in favorable neurological outcome. Particularly in metastatic motor eloquent lesion, motor function appears to be preserved after surgery. Clin. Anat. 29:925-931, 2016. © 2016 Wiley Periodicals, Inc.

Darbepoetin-α accelerates neovascularization and engraftment of extrahepatic colorectal metastases.

PURPOSE: Erythropoietin and its analogue darbepoetin (DPO)-α have been shown to improve liver function and regeneration after partial hepatectomy (Phx). However, previous experimental studies have also shown that DPO significantly enhances Phx-induced engraftment of colorectal liver metastases by increasing neovascularization and tumor cell proliferation. Therefore, the present study analyzed whether DPO affects engraftment and neovascularization of extrahepatic colorectal metastases after major hepatectomy. METHODS: Green fluorescent protein-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Animals received a single dose of DPO (10 µg/kg body weight) at the day of tumor cell implantation (day 0). Phosphate-buffered saline-treated animals served as controls. To study whether the effect of DPO is influenced by Phx, additional animals with and without DPO treatment underwent 70% Phx at day 0. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied repetitively over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry. RESULTS: In nonhepatectomized animals, DPO significantly accelerated tumor cell engraftment and slightly enhanced tumor neovascularization. Tumor cell migration and host tissue infiltration were not affected by DPO. In hepatectomized animals, DPO slightly enhanced tumor growth and significantly accelerated tumor neovascularization, but did not affect tumor cell migration and infiltration. CONCLUSION: The present study indicates that DPO accelerates extrahepatic engraftment of colorectal cancer cells, most probably by stimulating the process of neovascularization.

Endoscopic-Assisted Microsurgical Meningioma Resection in the Skull Base via Minicraniotomy: Is There a Difference in Radicality and Outcome between Anterior Skull Base and Posterior Fossa?

Background: Keyhole-based approaches are being explored for skull base tumor surgery; aiming for reduced complications while maintaining resection success rates. This study evaluates skull base meningiomas resected using an endoscopic-assisted microsurgical keyhole approach, comparing outcomes with standard procedures. Methods: Between 2013 and 2019; 71 out of 89 patients were treated using an endoscopic-assisted microsurgical procedure. A total of 42 meningiomas were localized at the anterior skull base and 29 in the posterior fossa. The surgical techniques and use of an endoscope were analyzed and compared in terms of complications, surgical radicality, outcome, and recurrences in the patients' follow-up. Results: The two different cohorts yielded similar rates of GTR (anterior skull base: 80% versus posterior fossa: 82%). The complication rate was 31% for the posterior fossa and 16% for the anterior skull base. An endoscope was used in 79% of all cases. Tumor remnants were detected by means of endoscopic visualization in 58.6% of posterior fossa and 33% of anterior skull base meningiomas. The statistical analysis revealed significantly higher benefits from endoscope use in the posterior fossa cohort (p < 0.05). Conclusions: The results revealed that endoscopy was beneficial in both locations. The identification of remnant tumor tissue and the benefit of endoscopy were clearly higher in the posterior fossa. Endoscopic assistance is a very helpful tool for increasing radicality, providing a better anatomical overview during surgery, and better identifying remnant tumor tissue in skull base meningioma surgery.

Development and Evaluation of an MRI Artifact-Free Aneurysm Clip.

BACKGROUND AND OBJECTIVES: The digital subtraction angiography is still the gold standard in the follow-up after aneurysm surgery, although it remains a repeating invasive technique with accumulating X-ray exposure. An alternative magnetic resonance angiography has the disadvantage of metal-related artifacts. A metal-free aneurysm clip could overcome this problem. Recent advances in manufacturing technologies of fiber-reinforced plastics might allow developing a prototype of a metal-free clip. METHODS: The prototype was formed out of carbon fiber-reinforced polyetheretherketone (CF-PEEK) in accordance with the standard clip design. In vivo and in vitro studies were performed to analyze the central nervous system biocompatibility. The prototype was tested in a phantom in a 3 T MRI scanner and microtomography scanner. For in vivo assessment, the left renal artery of rats was either ligated with a suture, clipped with a regular titanium clip or with the CF-PEEK prototype clip. The animals underwent standard MRI sequences and magnetic resonance angiography and assessment by a blinded neuroradiologist. RESULTS: Phantom studies showed no signs of artifacts. The prototype showed a reliable clamping and reopening after clip application, although the clamping force was reduced. In vivo studies showed a successful occlusion of the renal artery in all cases in the magnetic resonance angiography. Clip artifacts were statistically significant reduced in the prototype group (P < .01). CF-PEEK showed no signs of impaired biocompatibility compared with the titanium samples in vitro and in vivo. CONCLUSION: Former attempts of metal-free aneurysm clips did not meet the criteria of the standard clip design. In this study, the practicability of this new CF-PEEK artifact-free aneurysm clip has been proven. The further fabrication developments should overcome the problem of a reduced clamping force in the future. After clinical approval, it will improve the magnetic resonance image quality and might help to reduce the amount of digital subtraction angiography in the follow-up.

Darbepoetin-α promotes neovascularization and cell proliferation in established colorectal liver metastases.

BACKGROUND: The erythropoietin-analogue darbepoetin-α (DPO) improves liver function and regeneration after hepatectomy (Phx), however, also enhances Phx-induced tumor cell engraftment and neovascularization. Because it is unknown whether DPO also enhances the growth of established tumors, we herein studied the effect of DPO on established colorectal liver metastases after Phx. METHODS: CT26.WT cells were implanted into the liver of BALB/c mice. Five days after tumor establishment, animals underwent 50% Phx and received 10 µg/kgBW DPO or saline. Non-Phx animals with DPO or saline-treatment served as controls. Seven days after Phx tumors were analyzed regarding blood vessel formation, leukocyte adhesion, cell proliferation, apoptotic cell death, and growth using intravital fluorescence microscopy, histology, and immunohistochemistry. RESULTS: The growth of established colorectal liver metastases was slightly stimulated after DPO-treatment in hepatectomized and non-hepatectomized animals. However, tumor vessel formation and tumor cell proliferation were significantly enhanced after DPO-treatment in hepatectomized and non-hepatectomized mice compared with controls. Apoptotic cell death and leukocyte-endothelial cell interaction were significantly reduced after DPO-treatment. CONCLUSION: Our study indicates that DPO-treatment promotes neovascularization and cell proliferation in established colorectal liver metastases of hepatectomized and non-hepatectomized mice. DPO-application in patients with colorectal liver metastases might promote tumor progression and should therefore be avoided.

Evaluation of a fluorescence endoscope in murine in-vivo auto-fluorescence glioma models.

INTRODUCTION: The value of extended and radical resection of high grade gliomas remains controversial, but the neurosurgical procedure is still vital for effective cancer treatment. Fluorescence guided surgery provides aggressive resection within the tumor margins even on microscopic levels. Aim of this study was to evaluate if a new developed fluorescence endoscope can improve intraoperative vision and tumor delineation. METHODS: An autofluoresence C6 glioma cell line was established via GFP-transfection. These GFP-C6 glioma cells were transplanted both in a dorsal skinfold chamber of the mouse and orthotopically in a cranial window chamber of the mouse. After five days, tumors were examinated by intravital fluorescence microscopy, a standard fluorescence operation microscope and a fluorescence endoscope. Images were compared in terms of visualization, magnification and delineation of tumor cells from host tissue. RESULTS: The fluorescence endoscope showed improved image quality and higher magnifications compared to the operation microscope. Even smallest tumor extensions were visualized by the fluorescence endoscope nearly reaching the quality of an intravital fluorescence microscope. CONCLUSIONS: In summary better visualization can improve the intraoperative decision making of the surgeons. So endoscopic assistance can be seen as a promising tool for the fluorescence guided resection of high grade gliomas in the next years.

Fluorescence image-guided resection of intracranial meningioma: an experimental in vivo study on nude mice.

INTRODUCTION: The use of photodynamic agents in malignant cranial tumor surgery is quite common. For example five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Until today there is no comparable selective fluorescent substance available for meningiomas. Nevertheless, there is a demand for intraoperative fluorescent identification of e.g. invasive skull base meningiomas to increase radicality. This study was established to investigate fluorescent image-guided resection with somatostatin receptor labelled fluorescence dye for intracranial meningioma in the nude mice. METHODS: Primary meningioma cell culture samples were stereotactically implanted subdural into 20 nude mice. 90 days after inoculation of the cells, a cranial MRI with contrast agent revealed tumor growth. After detection of tumor mass in MRI, FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide was injected intravenously and tumor mass was hereafter resected under visualization via fluorescence microscope and endoscope. After attempted total resection, animal were sacrificed brain slices were obtained and histologically analysed to verify the resection extent. RESULTS: In 18 mice tumor growth was detected in MRI after 90 days of inoculation. The tumor mass could be clearly identified with fluorescence microscope and endoscope after injecting FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide. The tumor margins could be better visualized. After fluorescence-guided resection no remaining tumor could be identified in histological analysis. CONCLUSIONS: This study describes for the first time the use of FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide and demonstrates its value of fluorescent identification of meningioma cells in vivo. Furthermore, the authors established a new experimental animal model for fluorescence meningioma surgery.

Preoperative Navigated Transcranial Magnetic Stimulation Improves Gross Total Resection Rates in Patients with Motor-Eloquent High-Grade Gliomas: A Matched Cohort Study.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is an established, noninvasive tool to preoperatively map the motor cortex. Despite encouraging reports from few academic centers with vast nTMS experience, its value for motor-eloquent brain surgery still requires further exploration. OBJECTIVE: To further elucidate the role of preoperative nTMS in motor-eloquent brain surgery. METHODS: Patients who underwent surgery for a motor-eloquent supratentorial glioma or metastasis guided by preoperative nTMS were retrospectively reviewed. The nTMS group (n = 105) was pair-matched to controls (non-nTMS group, n = 105). Gross total resection (GTR) and motor outcome were evaluated. Subgroup analyses including survival analysis for WHO III/IV glioma were performed. RESULTS: GTR was significantly more frequently achieved in the entire nTMS group compared to the non-nTMS group (P = .02). Motor outcome did not differ (P = .344). Bootstrap analysis confirmed these findings. In the metastases subgroup, GTR rates and motor outcomes were equal. In the WHO III/IV glioma subgroup, however, GTR was achieved more frequently in the nTMS group (72.3%) compared to non-nTMS group (53.2%) (P = .049), whereas motor outcomes did not differ (P = .521). In multivariable Cox-regression analysis, prolonged survival in WHO III/IV glioma was significantly associated with achievement of GTR and younger patient age but not nTMS mapping. CONCLUSION: Preoperative nTMS improves GTR rates without jeopardizing neurological function. In WHO III/IV glioma surgery, nTMS increases GTR rates that might translate into a beneficial overall survival. The value of nTMS in the setting of a potential survival benefit remains to be determined.

The endoscopic surgical resection of intrasellar lesions conserves the hormonal function: a negative correlation to the microsurgical technique.

BACKGROUND: The endonasal endoscopic approach is still currently under investigation for sellar tumor surgery: a higher resection rate is to be expected and complications should be minimized. The authors report their surgical results of endonasal endoscopic neurosurgery with special focus on postoperative hypopituitarism in comparison to microsurgical procedures. METHODS: Sixty patients received endoscopic endonasal transsphenoidal procedures for sellar pathologies. All patients were followed up prospectively. A second group of 60 patients received microsurgical transsphenoidal procedures for sellar pathologies in our neurosurgical department before and were prospectively followed until now. Special attention was paid to hormonal insufficiency and medical substitution. RESULTS: Sixty-eight percent (41 of 60) of the patients who underwent microsurgical procedures showed a new persisting pituitary insufficiency postoperatively. Twenty-three patients (55.5%) were substituted with thyroxine, hydrocortisone and sexual hormones and one patient (2.5%) also with ADH cause of global pituitary insufficiency. In 19 cases without any hormonal insufficiency after microsurgical procedures nine patients (47%) showed remnant tumor in follow-up MRI. The patients who underwent endoscopic procedures for pituitary adenomas revealed significant (P<0.01) less new persistent hormonal insufficiency with 13% of all cases (8/60). Five patients (62.5%) were substituted with thyroxine and hydrocortisone, two patients (25%) substituted with thyroxine, hydrocortisone and sexual hormones and one patient also with ADH because of global pituitary insufficiency. Thereby, in follow-up MRI and hormonal testing, radical tumor resection was detected in 92% in the endoscopic group. CONCLUSIONS: This study seems to indicate that a better intraoperative identification and preservation of pituitary gland is possible in endoscopic transsphenoidal surgery with consecutive lower postoperative hypopituitarism rate.

Imaging of Microhemodynamics in Peripheral Nerves by Contact Endoscope.

BACKGROUND: Entrapment neuropathies include a wide field of locations. In most cases, the microsurgical decompression is still the therapy of choice. However, the role of venous stasis and ischemia is still discussed controversially. Here the authors evaluated the visualization of microvessels and the microperfusion at peripheral nerves with a contact endoscope during the surgical decompression for the first time. METHODS: Eight patients were subjected to endoscopic or endoscopically assisted peripheral nerve decompression. In 3 patients with nerve tumors, the tumor carrying nerve was inspected endoscopically proximal and distal to the tumor site before and after resection. Microcirculation was assessed by a contact endoscope, allowing a 150-fold magnification, at superficial areas proximal and distal to the compression site. The electronically stored records were analyzed retrospectively using image processing software. Vessel diameter, red blood cell velocity, and blood flow, before and after decompression, were extracted. RESULTS: The contact endoscope was easy to handle intraoperatively without problems. All minimally invasive procedures were performed without complications. In the offline computer-assisted analysis, single arterioles and veins were visualized showing decreased red blood cell velocity prior to decompression. After surgical treatment, a statistically significant increase of blood flow was observed. CONCLUSIONS: Basically, the application of a contact endoscope for visualization of peripheral nerves' microcirculation is feasible. The observed effect of increased blood flow after decompression should be compared with the clinical outcome in a further prospective randomized study.

Visualization and Identification of the Pituitary Gland Tissue in Endonasal Pituitary Surgery: Is There a Difference Between High-Definition Endoscopy and Microscopy?

OBJECTIVE: Neurosurgical techniques for the treatment of sellar pathologies have been evolving continuously over recent decades. In addition to the innovation of approaches and surgical techniques, this progress yielded to the application of modern operative technologies. The introduction of high-definition (HD) cameras for endoscopic systems has shown good results in endonasal pituitary surgery. The aim of this study was to assess endoscopic HD image quality in comparison with microscopic visualization. METHODS: All pituitary surgeries were performed via an endonasal approach in the endoscopic technique. For each comparison, pituitary gland tissue was predefined intraoperatively. A resident was randomly required to identify this tissue either using HD endoscopic or microscopic visualization through the endonasal approach. Subjective image quality was requested with a questionnaire. Furthermore, the illuminance level of the endoscope and microscope was measured in the sellar region in an experimental setup. RESULTS: Thirty-five procedures were performed and included in this comparison. Of the 35 procedures, 74% of gland tissue cases were identified correctly under endoscopic visualization, whereas it was identified correctly under microscopic visualization in 8% (P < 0.05). There was no significant correlation of experience and intraoperative results in cases of the microscopic (r = -0.15) or endoscopic visualization (r = 0.22). The identification of tissue in the depth of the surgical field via endoscopic HD visualization was thought to be superior to the microscope in 86.8%. Both modalities were assessed equal in 10.4%. Microscopic visualization was rated superior in 2.8% of all cases. There was a significant superiority of endoscopic visualization (P < 0.05). The mean lux level for endoscopic visualization of the sellar region was 221,000. The mean lux level decreased significantly by 66% to 241,000 lx with 350-mm distance and by 60% to 141,000 lx with 450-mm distance because of the positioning of the microscope in front of the head form to visualize the surgical field at the sellar region. CONCLUSIONS: HD endoscopic visualization accounted for significantly more reliable identifications of pituitary gland tissue in comparison with the microscope in the presented setting. The subjective impression of image quality is better with HD endoscopes. The goal of further studies should be to identify if these findings would also result in improved surgical outcome in short-term and long-term follow-up.

[The use of Idarucizumab in intracerebral bleeding - a case report]. / Der Einsatz von Idarucizumab bei intrazerebraler Blutung ­ Ein Fallbericht.

HISTORY AND CLINICAL FINDINGS: 82-year old male patient suspected of having cerebral hemorrhage under anticoagulation therapy with Dabigatran due to atrial fibrillation. INVESTIGATIONS: CT scan showed bilateral chronic subdural hematomas with fresh blood in left-subdural hematoma and midline shift. Laboratory analysis shows only a moderately high Dabigatran level but thrombin time was high out of range. DIAGNOSIS: Fall-related intracerebral haemorrhage and subdural hematoma under anticoagulation therapy. THERAPY AND COURSE: Neurosurgical hematoma evacuation and trepanation after preoperative use of Idarucizumab as an antidote for Dabigatran to stop anticoagulative effects and secure normal bleeding conditions, led to reduced midline shift. We started heparin-based anticoagulation first followed by Dabigatran again in clinical steady state and after rehabilitation with neurologically low-grade residuals.

Management of severe intraoperative hemorrhage during intraventricular neuroendoscopic procedures: the dry field technique.

OBJECTIVE: The unexpected intraoperative intraventricular hemorrhage is a rare but feared and life-threatening complication in neuroendoscopic procedures because of loss of endoscopic vision. The authors present their experience with the so-called "dry field technique" (DFT) for the management of intraventricular hemorrhages during purely endoscopic procedures. This technique requires the aspiration of the entire intraventricular CSF to achieve clear visualization of the bleeding source. METHODS: More than 500 neuroendoscopic intraventricular procedures were retrospectively analyzed over the last 24 years for documented severe hemorrhages, which were treated by the application of the DFT. RESULTS: The technique was required in 6 cases, including tumor resection/biopsy, cyst resection, and intraventricular lavage. Additionally, the technique was applied as part of the planned strategy in 3 cases of endoscopic tumor removal. The hemorrhage was stopped in all cases and no associated postoperative deficits occurred. CONCLUSIONS: Although severe hemorrhages are rare, the neurosurgeon needs to be aware of them and has to establish strategies for their management. Most hemorrhages can be stopped by constant irrigation and coagulation. In the other rare cases, the DFT is a safe, reliable technique and can be easily incorporated into endoscopic surgery.

Promoter methylation of RB1, P15, P16, and MGMT and their impact on the clinical course of pilocytic astrocytomas.

Promoter methylation of P15, P16, RB transcriptional corepressor 1 (RB1) and O-6-methylguanine-DNA methyltransferase (MGMT) impacts the prognosis of numerous glioma subtypes. However, whether promoter methylation of these genes also has an impact on the clinical course of pilocytic astrocytoma remains unclear. Using methylation-specific polymerase chain reaction, the methylation status of the tumor suppressor genes P15, P16, RB1, and MGMT in pilocytic astrocytomas (n=18) was analyzed. Immunohistochemical staining for the R132H mutation of the isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1) gene was performed. Clinical data including age, gender, localization of tumor, extent of resection, treatment modality, progression-free survival and overall survival were collected. The methylation index for P15, P16, RB1 and MGMT was 0.0, 0.0, 5.6% (1/18) and 44.5% (8/18), respectively. If the MGMT promoter was methylated, the probability of relapse and second subsequent therapy was significantly increased (P=0.019). The one patient with methylation of P15 demonstrated a poor clinical course. The pilocytic astrocytomas of all 18 patients revealed wild-type IDH1. Clinically, there was a significant correlation of subtotal resection with the occurrence of relapse (P=0.005) and of the localization of the tumor with the extent of resection (P=0.031). Gross total resection was achieved significantly more often in pediatric patients than in adult patients (P=0.003). Adult patients demonstrated more relapses following the first tumor resection (P=0.001). The present study indicates that methylation of MGMT is associated with a poor clinical course and represents an age-independent risk factor for an unfavorable outcome. Other influential factors of outcome were the age of the patient and extent of resection.