Exploring complications following cranioplasty after decompressive hemicraniectomy: A retrospective bicenter assessment of autologous, PMMA and CAD implants.

Cranioplasty (CP) after decompressive hemicraniectomy (DHC) is a common neurosurgical procedure with a high complication rate. The best material for the repair of large cranial defects is unclear. The aim of this study was to evaluate different implant materials regarding surgery related complications after CP. Type of materials include the autologous bone flap (ABF), polymethylmethacrylate (PMMA), calcium phosphate reinforced with titanium mesh (CaP-Ti), polyetheretherketone (PEEK) and hydroxyapatite (HA). A retrospective, descriptive, observational bicenter study was performed, medical data of all patients who underwent CP after DHC between January 1st, 2016 and December 31st, 2022 were analyzed. Follow-up was until December 31st, 2023. 139 consecutive patients with a median age of 54 years who received either PMMA (56/139; 40.3%), PEEK (35/139; 25.2%), CaP-Ti (21/139; 15.1%), ABF (25/139; 18.0%) or HA (2/139; 1.4%) cranial implant after DHC were included in the study. Median time from DHC to CP was 117 days and median follow-up period was 43 months. Surgical site infection was the most frequent surgery-related complication (13.7%; 19/139). PEEK implants were mostly affected (28.6%; 10/35), followed by ABF (20%; 5/25), CaP-Ti implants (9.5%; 2/21) and PMMA implants (1.7%, 1/56). Explantation was necessary for 9 PEEK implants (25.7%; 9/35), 6 ABFs (24.0%; 6/25), 3 CaP-Ti implants (14.3%; 3/21) and 4 PMMA implants (7.1%; 4/56). Besides infection, a postoperative hematoma was the most common cause. Median surgical time was 106 min, neither longer surgical time nor use of anticoagulation were significantly related to higher infection rates (p = 0.547; p = 0.152 respectively). Ventriculoperitoneal shunt implantation prior to CP was noted in 33.8% (47/139) and not significantly associated with surgical related complications. Perioperative lumbar drainage, due to bulging brain, inserted in 38 patients (27.3%; 38/139) before surgery was protective when it comes to explantation of the implant (p = 0.035). Based on our results, CP is still related to a relatively high number of infections and further complications. Implant material seems to have a high effect on postoperative infections, since surgical time, anticoagulation therapy and hydrocephalus did not show a statistically significant effect on postoperative complications in this study. PEEK implants and ABFs seem to possess higher risk of postoperative infection. More biocompatible implants such as CaP-Ti might be beneficial. Further, prospective studies are necessary to answer this question.

Simultaneous Interference with HER1/EGFR and RAC1 Signaling Drives Cytostasis and Suppression of Survivin in Human Glioma Cells in Vitro.

We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succinimidyl ester was performed in order to determine the induction of apoptosis, necrosis or cytostasis in established and primary cultured glioblastoma cells. Moreover, expression of Ki-67 was determined by immunofluorescence, and the expression of cell cycle proteins was analysed by Western blot. Our data show that combined treatment with erlotinib and NSC23766 resulted in a reduced number of cell divisions, a significantly decreased Ki-67 expression, increased apoptosis and autophagy when compared to single agent treatments. On the molecular level, concomitant treatment with both agents resulted in a pronounced downregulation of cyclin D1, cyclin-dependent kinases 2, 4 and 6, as well as of survivin when compared to treatments with either agent alone. In conclusion, we demonstrate that combined treatment of human glioma cell lines in vitro with erlotinib and NSC23766 markedly inhibits cell division, induces apoptosis independent of caspase-3 activation and induces autophagy concomitant with suppression of survivin.

Intraoperative magnetic resonance imaging.

Intraoperative magnetic resonance imaging is a widely accepted method for resection control of glial tumors. Increasingly, it is also used during the resection of skull base tumors. Several studies have independently demonstrated an increase in the extent of resection in these tumors with improved prognosis for the patients. Technical innovations combined with the easier operation of this imaging modality have led to its widespread implementation. The development of digital image processing has also brought other modalities such as ultrasound and computed tomography to the focus of skull base surgery.

[Intraoperative navigation, with focus on the skull base]. / Intraoperative Navigation mit Fokus auf der Schädelbasis.

Intraoperative navigation systems are widely used in ENT, oral and maxillofacial, and neurosurgery. The benefits of such systems have been demonstrated in various applications, including intracranial and skull base surgery. Intraoperative shift, "brain shift" and changes in anatomy caused by the surgical procedure itself impair the accuracy of navigation and represent factors limiting its application, particularly in glioma and metastatic brain surgery. For this reason, intraoperative imaging was incorporated into neurosurgery. A specific application of navigation is thus skull base surgery, where shifts are often negligible due to the bony structures in which pathologies are embedded. Development of new systems with seamless integration into the operative workflow propagated routine use of navigation in neuro- and ENT surgery. Navigation proved especially helpful in interdisciplinary surgery with pathologies located in anatomic regions where competences of different surgical disciplines overlap, as in the skull base. While this increased radicality in tumour resection, there was a high risk of morbidity. The integration of electrophysiological function monitoring served to preserve function and reduce morbidity, and has led to less invasive and radical strategies in skull base surgery. New radiosurgical methods to adjuvantly treat possible tumour remnants have also supported this development. Systems allowing resection borders to be marked in the navigational coordinates would enable direct linking of these data to radiotherapy planning and better interpretation of follow-up imaging. Navigation is thus a valuable tool supporting interdisciplinary cooperation in skull base surgery for the benefit of patients.

[Intraoperative magnetic resonance imaging. Fifteen years' experience in the neurosurgical hybrid operating suite]. / Intraoperative Magnetresonanztomographie. Erfahrungen aus 15 Jahren Hybridoperationssaal in der Neurochirurgie.

Intraoperative magnetic resonance imaging was established 15 years ago due to special requirements for the resection of cerebral gliomas. Several studies have independently shown an increase of the extent of resection of the tumor and also an improved survival of the patients. Technical innovations combined with an easier operation of this imaging modality led to widespread implementation of this method. The introduction of functional and metabolic imaging opened up new prospects of further improving the therapeutic outcome.

Lows and highs: 15 years of development in intraoperative magnetic resonance imaging.

Intraoperative magnetic resonance imaging (ioMRI) during neurosurgical procedures was first implemented in 1995. In the following decade ioMRI and image guided surgery has evolved from an experimental stage into a safe and routinely clinically applied technique. The development of ioMRI has led to a variety of differently designed systems which can be basically classified in one- or two-room concepts and low- and high-field installations. Nowadays ioMRI allows neurosurgeons not only to increase the extent of tumor resection and to preserve eloquent areas or white matter tracts but it also provides physiological and biological data of the brain and tumor tissue. This article tries to give a comprehensive review of the milestones in the development of ioMRI and neuronavigation over the last 15 years and describes the personal experience in intraoperative low and high-field MRI.

Image guided aneurysm surgery in a Brainsuite® ioMRI Miyabi 1.5 T environment.

OBJECTIVE: Current literature only gives sparse account of aneurysm surgery in an intraoperative MRI environment. After installation of a BrainSuite(®) ioMRI Miyabi 1.5 T at our institution the aim of the present preliminary study was to evaluate feasibility, pros and cons of aneurysm surgery in this special setting. MATERIAL AND METHODS: Since February 2009, during a 3 months period we performed elective image guided aneurysm surgery in 4 ACM and 1 ACOM aneurysm (four patients) in this ioMRI setting. The patients' heads were rigidly fixed in the Noras 8-Channel OR Head Coil. Our imaging protocol included MP-RAGE, T2-TSE axial, TOF-MRA and diffusion-/perfusion-imaging immediately before surgery and after clip application. Presurgical 3D-planning was performed using the iPlan®-Software. RESULTS: All five aneurysms were operated without temporary clipping. There were no intra- or postoperative complications. Patient positioning and head fixation with the integrated Noras Head Clamp was feasible, but there were significant limitations particularly with regard to more complex approaches and patient physiognomy. Image quality especially TOF-MRA was good in 4, insufficient in 1 aneurysm. Presurgical planning especially vessel extraction from TOF-MRA was possible but certainly needs significant future improvement. Diffusion- and perfusion weighted examinations yielded good image quality. CONCLUSION: Our limited experience is encouraging so far. Further improvement particularly concerning flexibility of patient positioning and presurgical 3D-planning for vascular procedures is most necessary. As a future perspective image guided aneurysm surgery in an ioMRI-environment may be helpful especially in complex aneurysms and provide neurosurgeons and neuroanaesthesiologists with additional information about cerebral haemodynamics and perfusion pattern in the vascular territory distal to the target vessel.

CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells.

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.

Surgically induced intracranial contrast enhancement: potential source of diagnostic error in intraoperative MR imaging.

BACKGROUND AND PURPOSE: Intraoperative MR imaging is being used increasingly during neurosurgical interventions. The aim of this study was to describe and classify different forms of surgically induced intracranial contrast enhancement observed during intraoperative MR examinations. METHODS: A total of 51 intraoperative MR examinations were performed to assess the extent of brain tumor removal. The intraoperative MR results (T1-weighted images, unenhanced and obtained serially after the IV administration of paramagnetic contrast material) were compared with preoperative and early postoperative MR findings. Animal experiments were conducted to obtain further evidence of the mechanism of surgically induced contrast enhancement. RESULTS: Four different types of surgically induced contrast enhancement were found: meningeal enhancement, increased enhancement of the choroid plexus, delayed enhancement at the resection margins, and immediate intraparenchymal contrast enhancement. The types of surgically induced contrast enhancement differ regarding their location, configuration, and time course. Their potential to be confused with contrast-enhancing, residual tumor also varies. Three of the four types of surgically induced contrast enhancement were reproducible in an animal model. CONCLUSION: Surgically induced contrast enhancement is a potential source of error in intraoperative MR imaging. Careful analysis of the location, configuration, and time course of intraoperatively observed intracranial enhancement is critical to avoid confusing surgically induced contrast enhancement with contrast-enhancing, residual tumor.

Monocrystalline iron oxide nanoparticles: possible solution to the problem of surgically induced intracranial contrast enhancement in intraoperative MR imaging.

BACKGROUND AND PURPOSE: Intraoperative MR imaging is increasingly being used to control the extent of surgical resection; however, surgical manipulation itself causes intracranial contrast enhancement, which is a source of error. Our purpose was to investigate the potential of monocrystalline iron oxide nanoparticles (MIONs) to solve this problem in an animal model. METHODS: In male Wistar rats, surgical lesions of the brain were produced. The animals underwent MR examination immediately afterward. In the first group, a paramagnetic contrast agent was administered, whereas the second group of animals received MIONs 1 day before surgery. In a third group of animals, malignant glioma cells were stereotactically implanted in the caudoputamen. Two weeks later, MIONs were IV injected and the tumor was (partially) resected. Immediately after resection, MR examination was performed to determine the extent of residual tumor. RESULTS: Surgically induced intracranial contrast enhancement was seen in all animals in which a paramagnetic contrast agent was used. Conversely, when MIONs had been injected, no signal changes that could be confused with residual tumor were detected. In the animals that had undergone (partial) resection of experimental gliomas, MR assessment of residual tumor was possible without any interfering surgically induced phenomena. CONCLUSION: Because MIONs are stored in malignant brain tumor cells longer than they circulate in the blood, their use offers a promising strategy to avoid surgically induced intracranial contrast enhancement, which is known to be a potential source of error in intraoperative MR imaging.

Intraoperative MR imaging increases the extent of tumor resection in patients with high-grade gliomas.

BACKGROUND AND PURPOSE: MR is being used increasingly as an intraoperative imaging technique. The purpose of this study was to test the hypothesis that intraoperative MR imaging increases the extent of tumor resection, thus improving surgical results in patients with high-grade gliomas. METHODS: Thirty-eight patients with intracranial high-grade gliomas underwent 41 operations. Using a neuronavigation system, tumors were resected in all patients to the point at which the neurosurgeon would have terminated the operation because he thought that all enhancing tumor had been removed. Intraoperative MR imaging (0.2 T) was performed, and surgery, if necessary and feasible, was continued. All patients underwent early postoperative MR imaging (1.5 T). By comparing the proportions of patients in whom complete resection of all enhancing tumor was shown by intraoperative and early postoperative MR imaging, respectively, the impact of intraoperative MR imaging on surgery was determined. RESULTS: Intraoperative MR imaging showed residual enhancing tumor in 22 cases (53.7%). In 15 patients (36.6%), no residual tumor was seen, whereas the results of the remaining four intraoperative MR examinations (9.7%) were inconclusive. In 17 of the 22 cases in which residual tumor was seen, surgery was continued. Early postoperative MR imaging showed residual tumor in eight patients (19.5%) and no residual tumor in 31 cases (75.6%); findings were uncertain in two patients (4.9%). The difference in the proportion of "complete removals" was statistically highly significant (P = .0004). CONCLUSION: Intraoperative MR imaging significantly increases the rate of complete tumor removal. The rate of complete removal of all enhancing tumor parts was only 36.6% when neuronavigation alone was used, which suggests the benefits of intraoperative imaging.

Clinical evaluation and follow-up results for intraoperative magnetic resonance imaging in neurosurgery.

OBJECTIVE: The use of intraoperative magnetic resonance imaging (MRI) in neurosurgery has increased rapidly, and a variety of concepts have recently been presented. Although the feasibility of the procedure has been demonstrated repeatedly, no conclusive analysis of its effects on the surgical procedures, the extent of tumor removal, and outcomes, or its possible problems, has been performed. METHODS: Of 242 operations performed with intraoperative MRI, 97 procedures for supratentorial glioma treatment were analyzed with respect to intraoperative imaging results and postoperative outcomes. Analysis of the images included assessment of imaging artifacts, image quality, and extent of tumor removal. Patients were monitored to determine radiological progression, survival times, postoperative complications, and morbidity rates. RESULTS: No intraoperative complications related to the imaging procedure were observed. Image quality was good or fair in 85.5% of the cases. Different types of surgically induced imaging changes could be identified. In 56 cases, resection was continued using navigation with intraoperative MRI data sets (rereferencing accuracy, 0.9 mm). For high-grade gliomas, the percentage of cases in which residual tumor was identified by MRI could be significantly reduced from 62% intraoperatively to 33% postoperatively, which was paralleled by a significant increase in survival times for patients without residual tumor. Complication and morbidity rates were within the ranges reported for other studies. CONCLUSION: Intraoperative MRI is safe and allows reliable updating of neuronavigational data, with compensation for brain shifting. Surgically induced imaging changes, which have been identified as a possible problem with intraoperative MRI in general, necessitated comparisons with preoperative scans and require future attention. The extent of tumor removal and survival times were increased significantly. Overall, patients seemed to benefit from the method.

Intraoperative diagnostic and interventional magnetic resonance imaging in neurosurgery.

OBJECTIVE: The benefits of intraoperative magnetic resonance (MR) imaging for diagnostic and therapeutic measures are as follows: 1) intraoperative update of data sets for navigational systems, 2) intraoperative resection control of brain tumors, and 3) frameless and frame-based on-line MR-guided interventions. The concept of an intraoperative MR scanner in the sterile environment of operating theater is presented, and its advantages, disadvantages, and limitations are discussed. METHODS: A 0.2-tesla magnet (Magnetom Open; Siemens AG, Erlangen, Germany) inside a radiofrequency cabin with a radiofrequency-shielded sliding door was installed adjacent to one of the operating theaters. A specially designed patient transport system carried the patient in a fixed position on an air cushion to the scanner and back to the surgeon. RESULTS: In a series of 27 patients, intraoperative resection control was performed in 13 cases, with intraoperative reregistration in 4 cases. Biopsies, cyst aspirations, and catheter placements (mainly frameless) were performed under direct MR visualization with fast image sequences. The MR-compatible equipment and the patient transport system are safe and reliable. CONCLUSION: Intraoperative MR imaging is a safe and successful tool for surgical resection control and is clearly superior to computed tomography. Intraoperative acquisition of data sets eliminates the problem of brain shift in conventional navigational systems. Finally, on-line MR-guided interventional procedures can be performed easily with this setting. As with all MR systems, individual testing with phantoms, application of correction programs, and determination of the optimal amount of contrast media are absolute prerequisites to guarantee patient safety and surgical success.

Modified Headholder and operating table for intra-operative MRI in neurosurgery.

In order to facilitate intra-operative use of magnetic resonance imaging (MRI) in neurosurgery an MRI-compatible headholder was developed and adapted to a modified MR-couch simultaneously serving as tabletop for the operating table. To allow shock-free transport into the scanner the wheels of the operating table were replaced by an air cushion mechanism. In 75 procedures the system proved to be reliable and safe. Image quality was not impaired by the fixation device. With growing routine the transfer became straightforward, requiring approximately 10 min. Intra-operative MRI is thus made possible with minimal changes to the standard surgical environment. Its benefit however, still remains to be critically investigated.

The benefit of neuronavigation for neurosurgery analyzed by its impact on glioblastoma surgery.

Neuronavigation, today a routine method in neurosurgery, has not yet been systematically assessed in direct comparison with conventional microsurgical techniques. The aim of the present study was the direct comparison of the impact of neuronavigation on glioblastoma surgery regarding time consumption, extent of tumor removal and survival. For each of 52 patients operated for primary glioblastoma with neuronavigation, a patient operated on without navigation was matched. Completeness of tumor resection, including volumetric analysis, was examined by early post-operative MRI. Operating and survival times were obtained for all patients. At a rate of 86.5%, surgeons' opinions about neuronavigation were positive. Operating times were identical in the two groups, while preparation times were 30.4 min longer with navigation. Radiological radicality was achieved in 31% of navigation cases vs. 19% in conventional operations. The absolute and relative residual tumor volumes were significantly lower with neuronavigation. Radical tumor resection was associated with a highly significant prolongation in survival (median 18.3 vs. 10.3 months, p < 0.0001). Survival was longer in patients operated on using neuronavigation (median 13.4 vs. 11.1 months). Neuronavigation increases radicality in glioblastoma resection without prolonging operating time. Regarding the problem of brain shift, neuronavigation should be optimized by intraoperative real-time imaging.

Preoperative planning and intraoperative navigation in skull base surgery.

Experience with the commercially available, 3-D navigation systems Viewing Wand (ISG, Mississauga, Ontario, Canada) and SPOCS (Aesculap, Germany) in skull base surgery is presented. Having meanwhile been tested in over 60 clinical trials, the systems achieved an accuracy of < or = 2.7 mm which, at the moment, we deem sufficiently acceptable to proceed with their clinical evaluation. There was no difference in intraoperative accuracy between the mechanical and the optical navigation systems. The systems proved to be very helpful in identifying the extent of the tumours and in visualizing the proximity of vital structures. 3-D-planning, simulation and intraoperative navigation especially facilitates surgery in anatomically complicated situations, without risk of damaging neighbouring structures. The SPOCS (Surgical Planning and Orientation Computer System) revealed a considerably improved flexibility in handling and a better integration into the surgical procedure in comparison with the relatively inflexible and space-demanding Viewing Wand arm. Especially, the 'offset' function of the SPOCS offers the possibility of a virtual elongation of the instrument and thus, in combination with the on-line visualization of the corresponding images, of a 'look ahead' operation. By using computer-assisted simulation and navigation systems, we can expect quality improvement and risk reduction. More extensive and radical interventions seem possible.

Comparison of intraoperative MR imaging and 3D-navigated ultrasonography in the detection and resection control of lesions.

OBJECT: The authors undertook a study to compare two intraoperative imaging modalities, low-field magnetic resonance (MR) imaging and a prototype of a three-dimensional (3D)-navigated ultrasonography in terms of imaging quality in lesion detection and intraoperative resection control. METHODS: Low-field MR imaging was used for intraoperative resection control and update of navigational data in 101 patients with supratentorial gliomas. Thirty-five patients with different lesions underwent surgery in which the prototype of a 3D-navigated ultrasonography system was used. A prospective comparative study of both intraoperative imaging modalities was initiated with the first seven cases presented here. In 35 patients (70%) in whom ultrasonography was performed, accurate tumor delineation was demonstrated prior to tumor resection. In the remaining 30% comparison of preoperative MR imaging data and ultrasonography data allowed sufficient anatomical localization to be achieved. Detection of metastases and high-grade gliomas and intraoperative delineation of tumor remnants were comparable between both imaging modalities. In one case of a low-grade glioma better visibility was achieved with ultrasonography. However, intraoperative findings after resection were still difficult to interpret with ultrasonography alone most likely due to the beginning of a learning curve. CONCLUSIONS: Based on these preliminary results, intraoperative MR imaging remains superior to intraoperative ultrasonography in terms of resection control in glioma surgery. Nevertheless, the different features (different planes of slices, any-plane slicing, and creation of a 3D volume and matching of images) of this new ultrasonography system make this tool a very attractive alternative. The intended study of both imaging modalities will hopefully allow a comparison regarding sensitivity and specificity of intraoperative tumor remnant detection, as well as cost effectiveness.

Hemicraniectomy with dural augmentation in medically uncontrollable hemispheric infarction.

Surgical decompression to alleviate raised intracranial pressure has been reported repeatedly in the past decades in small series of patients. Only recently have there been indications from larger trials that surgical decompression may be beneficial in treating space-occupying hemispheric infarction. However, surgical requirements for the procedure to be effective have not yet been defined. Based on theoretical criteria, the authors operated on 43 patients with medically uncontrollable hemispheric infarctions. The craniectomies were planned to be as large as possible and performed in combination with a subtemporal decompression. Postoperative computerized tomography scans were evaluated for these criteria. The mean survival rate for the group of 43 patients was 72.1% and no surviving patient ended up in a vegetative state. The mean area of craniectomy was found to be 84.3 +/- 16.5 cm2 and the mean distance of the inferior craniectomy margin to the middle fossa was 1.8 +/- 1.3 cm. Comparison of survivors and nonsurvivors failed to show a significant difference in the size of craniectomy or the distance to the floor of the middle fossa. Compared with the reported 80% fatality rate for medically treated stroke patients, in this subgroup the outcome (72.1% survival rate) is remarkably good. The authors conclude that decompressive craniectomy is an effective treatment, able to reduce mortality, and to improve neurological outcome in patients with space-occupying cerebral infarction if the size of craniectomy is large enough. Nevertheless, there is a need for further investigation to identify patients who will benefit from surgery and predictors to optimize the timing of surgical intervention.