Craniectomy size and decompression of the temporal base using the altered posterior question-mark incision for decompressive hemicraniectomy.

The altered posterior question-mark incision for decompressive hemicraniectomy (DHC) was proposed to reduce the risk of intraoperative injury of the superficial temporal artery (STA) and demonstrated a reduced rate of wound-healing disorders after cranioplasty. However, decompression size during DHC is essential and it remains unclear if the new incision type allows for an equally effective decompression. Therefore, this study evaluated the efficacy of the altered posterior question-mark incision for craniectomy size and decompression of the temporal base and assessed intraoperative complications compared to a modified standard reversed question-mark incision. The authors retrospectively identified 69 patients who underwent DHC from 2019 to 2022. Decompression and preservation of the STA was assessed on postoperative CT scans and CT or MR angiography. Forty-two patients underwent DHC with the standard reversed and 27 patients with the altered posterior question-mark incision. The distance of the margin of the craniectomy to the temporal base was 6.9 mm in the modified standard reversed and 7.2 mm in the altered posterior question-mark group (p = 0.77). There was no difference between the craniectomy sizes of 158.8 mm and 158.2 mm, respectively (p = 0.45), and there was no difference in the rate of accidental opening of the mastoid air cells. In both groups, no transverse/sigmoid sinus was injured. Twenty-four out of 42 patients in the modified standard and 22/27 patients in the altered posterior question-mark group had a postoperative angiography, and the STA was preserved in all cases in both groups. Twelve (29%) and 5 (19%) patients underwent revision due to wound-healing disorders after DHC, respectively (p = 0.34). There was no difference in duration of surgery. Thus, the altered posterior question-mark incision demonstrated technically equivalent and allows for an equally effective craniectomy size and decompression of the temporal base without increasing risks of intraoperative complications. Previously described reduction in wound-healing complications and cranioplasty failures needs to be confirmed in prospective studies to demonstrate the superiority of the altered posterior question-mark incision.

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

The Genetic Basis of Moyamoya Disease.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a "puff of smoke" (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the  development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Bypass in neurosurgery-indications and techniques.

Since the introduction of cerebral bypass surgery by Professor Yasargil in 1967, a plethora of literature has been published on direct cerebral revascularization. Against this background, it is remarkable that at present, only three randomized controlled trials (RCTs) exist in the field, both dealing with extracranial to intracranial bypass surgery for flow augmentation in patients at risk to suffer ischemic or hemorrhagic stroke due to cerebrovascular disease. Next to flow augmentation, the other main indication for bypass surgery is to provide flow replacement following proximal vessel sacrifice for treatment of complex aneurysms or skull base tumors. The aim of this review was to provide a comprehensive overview of the literature regarding the indications and the techniques of cerebral bypass surgery for prevention of cerebral ischemia.

[Operative treatment of the degenerative cervical spine]. / Operative Versorgung der degenerativen Halswirbelsäule.

BACKGROUND: Degenerative alterations of the cervical spine often entail disc herniations and stenoses of the spinal canal and/or neural foramen. Mediolateral or lateral compression of nerve roots causes cervical radiculopathy, which is an indication for surgery in cases of significant motor deficits or refractory pain. Median canal encroachment may result in compression of the spinal cord and cervical myelopathy. Its natural history is typically characterized by episodic deterioration, so that surgical decompression is indicated in cases of clear myelopathic signs. OBJECTIVE: The aim of the present article is to outline the operative options for patients with cervical radiculopathy and myelopathy. Furthermore, we describe the operative complications and the outcome in these patients. MATERIAL AND METHODS: For this manuscript a systematic PubMed search was carried out, the papers were systematically analyzed for the best evidence and this was combined with the authors' experience. RESULTS AND CONCLUSION: Depending on the cervical pathology, the most prevalent surgical options for radiculopathy include anterior cervical discectomy and fusion (ACDF), cervical arthroplasty or posterior cervical foraminotomy. Cervical myelopathy may be decompressed by ACDF, corpectomy or posterior approaches like laminectomy plus instrumented fusion or laminoplasty. The outcome depends on the cervical pathology and the type of operation. Overall, in long-term follow-up studies the results of all surgical techniques on the cervical spine are generally considered to be very good, although specific patient characteristics are more suited for a particular approach.

Revision surgery for cervical artificial disc: Surgical technique and clinical results.

OBJECTIVE: Cervical artificial disc replacement (C-ADR) was developed with the goal of preserving mobility of the cervical segment in patients with degenerative disc disease. So far, little is known about experiences with revision surgery and explantation of C-ADRs. Here, we report our experience with revision the third generation, Galileo-type disc prosthesis from a retrospective study of two institutions. PATIENTS AND METHODS: Between November 2008 and July 2016, 16 patients with prior implantation of C-ADR underwent removal of the Galileo-type disc prosthesis (Signus, Medizintechnik, Germany) due to a call back by industry. In 10 patients C-ADR was replaced with an alternative prosthesis, 6 patients received an ACDF. Duration of surgery, time to revision, surgical procedure, complication rate, neurological status, histological findings and outcome were examined in two institutions. RESULTS: The C-ADR was successfully revised in all patients. Surgery was performed through the same anterior approach as the initial access. Duration of the procedure varied between 43 and 80min. Access-related complications included irritation of the recurrent nerve in one patient and mal-positioning of the C-ADR in another patient. Follow up revealed two patients with permanent mild/moderate neurologic deficits, NDI (neck disability index) ranged between 10 and 42%. CONCLUSIONS: Anterior exposure of the cervical spine for explantation and revision of C-ADR performed through the initial approach has an overall complication rate of 18.75%. Replacements of the Galileo-type disc prosthesis with an alternative prosthesis or conversion to ACDF are both suitable surgical options without significant difference in outcome.

Impact of sacropelvic fixation on the development of postoperative sacroiliac joint pain following multilevel stabilization for degenerative spine disease.

OBJECTIVE: We hypothesised, that the inclusion of the ilium for multilevel lumbosacral fusions reduces the incidence of postoperative sacroiliac joint (SIJ) pain. The primary objective of this study was to compare the frequency of postoperative SIJ pain in patients undergoing multilevel stabilization with and without sacropelvic fixation for multilevel degenerative spine disease. In addition, we aimed at identifying factors that may predict the worsening or new onset of postoperative SIJ pain. METHODS: A total of 63 patients with multisegmental fusion surgery with a minimum follow up of 12 months were evaluated. 34 patients received sacral fixation (SF group) and 29 patients received an additional sacropelvic fixation device (SPF group). Primary outcome parameters were changes in SIJ pain between the groups and the influence of pelvic parameters, the patient́s age, the patient́s body mass index (BMI) and the length of the stabilization on the SIJ pain. RESULTS: Between the two surgical groups there were no differences concerning age (p=0.3), BMI (p=0.56), length of follow up (p=0.96), length of the construct (p=0.56). In total 31.7% of the patients had a worsening/new onset of SIJ pain after surgery. An additional fixation of the SIJ with iliac screws or iliosacral plate did not have an influence on the SIJ pain (p=0.67). Likewise, pelvic parameters were not predictive for the outcome of the SIJ pain. Only an increased preoperative BMI correlated with a higher chance of a new onset of SIJ pain (p=0.037). CONCLUSION: In our retrospective study there was no influence of a sacropelvic fixation techniques on the SIJ pain in patients with multilevel degenerative spine disease after multilevel stabilization surgeries. The patients' BMI is the only preoperative factor that correlated with a higher incidence to develop postoperative SIJ pain, independently of the implantation of a sacropelvic fixation device.

Grading of moyamoya disease allows stratification for postoperative ischemia in bilateral revascularization surgery.

BACKGROUND: Moyamoya disease (MMD) may be graded based on DSA, the presence of ischemia in MRI and cerebrovascular reserve capacity allowing the prediction of ischemic symptoms in patients. Cerebral ischemia represents a severe complication in revascularization surgery. Focusing on different clinical features of hemodynamic impairment, MMD grading may allow prediction of ischemic complications. It was the aim to analyze whether MMD grading stratifies for ischemic complications in revascularization surgery for MMD. METHOD: In 37 MMD patients a bilateral, standardized, one-staged revascularization approach consisting of STA-MCA bypass/encephalomyosynangiosis (EMS) and single EMS on the contralateral hemisphere was performed. Clinical data including DSA, MRI and rCBF (Xenon-CT) studies were assessed and used for grading MMD. All patients were observed on the ICU for at least 24 h and received CT imaging on the first postoperative day and in case of neurological deterioration. Ischemic complications were analyzed until the day of discharge and at 6-month follow-up. RESULTS: Grading of MMD revealed 11 hemispheres (15 %) as grade I, 33 hemispheres (44 %) as grade II and 30 hemispheres (41 %) as grade III. Eight ischemic complications were observed (11 %). MMD grading demonstrated a significant correlation with ischemic complications: 0 complications in grade I, 3 in grade II (9 %) and 5 in grade III hemispheres (16 %; p < 0.05, Fisher's exact test). CONCLUSIONS: The proposed grading system allows to stratify for ischemic complications in MMD patients that receive bilateral, one-staged revascularization surgery. Future studies will have to investigate its use for predicting ischemic complications in other revascularization strategies for MMD.

F8-SIP mediated targeted photodynamic therapy leads to microvascular dysfunction and reduced glioma growth.

The extra domain A (ED A) of fibronectin has been identified as a tumor vessel specific neovascular marker in glioma. Antibody based vascular targeting against ED A of fibronectin allows precise accumulation of photosensitizer in glioma microvasculature and thereby promises to overcome drawbacks of current photodynamic therapy (PDT) for glioma treatment. Our aim was to characterize microcirculatory consequences of F8-small immunoprotein (SIP) mediated PDT by intravital microscopy (IVM) and to analyze the effects on glioma growth. For IVM SF126 glioma cells were implanted into dorsal skinfold-chamber of nude mice. PDT was performed after intravenous injection of photosensitizer (PS)-coupled F8-SIP or PBS (n = 4). IVM was performed before and after PDT for 4 days. Analysis included total and functional (TVD, FVD) vessel densities, perfusion index (PI), microvascular permeability and blood flow rate (Q). To assess tumor growth SF126 glioma cells were implanted subcutaneously. PDT was performed as a single and repetitive treatment after PS-F8-SIP injection (n = 5). Subcutaneous tumors were treated after uncoupled F8-SIP injection as control group (n = 5). PDT induced microvascular stasis and thrombosis with reduced FVD (24 h: 115.98 ± 0.7 vs. 200.8 ± 61.9 cm/cm(2)) and PI (39 ± 11 vs. 70 ± 10 %), whereas TVD was not altered (298 ± 39.2 vs. 278.2 ± 51 cm/cm(2)). Microvascular dysfunction recovered 4 days after treatment. Microvascular dysfunction led to a temporary reduction of glioma growth in the first 48 h after treatment with complete recovery 5 days after treatment. Repetitive PDT resulted in sustained reduction of tumor growth. F8-SIP mediated PDT leads to microvascular dysfunction and reduced glioma growth in a preclinical glioma model with recovery of microcirculation 4 days after treatment. Repetitive application of PDT overcomes microvascular recovery and leads to prolonged antiglioma effects.

Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach.

PURPOSE: Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope. METHODS: 22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss). RESULTS: 22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue. CONCLUSION: Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.

Ultra-early decompressive hemicraniectomy in aneurysmal intracerebral hemorrhage: a retrospective observational study.

BACKGROUND: The rupture of an intracranial aneurysm leading to subarachnoid hemorrhage (SAH) is frequently complicated by an extensive intracerebral hematoma (ICH). ICH represents a factor that worsens clinical outcome either due to early or delayed critical increase of intracranial pressure (ICP). Data on the management of aneurysmal ICH are lacking. Besides the securing of the ruptured aneurysm, there is the option of decompressive surgery to prevent secondary damage. The aim of this study was to analyze feasibility of decompressive hemicraniectomy (DHC) and the impact of timing in patients suffering from aneurysmal SAH with extensive ICH. METHODS: We retrospectively analyzed patients with aneurysmal ICH matched for age, sex, World Federation of Neurological Surgeons (WFNS) grade and ICH volume. All patients were treated via aneurysm clipping in conjunction with hematoma removal followed by either primary ultra-early DHC directly after admission or secondary, i.e. delayed DHC. We analyzed patient characteristics and management and the influence on postoperative care and outcome. Parameters were ICP, Glasgow Coma Scale (GCS), length of neurointensive care treatment and duration of mechanical ventilation. Outcome interviews were conducted as Extended Glasgow Outcome Scale (GOS-E). RESULTS: Nineteen consecutive patients with ruptured MCA-aneurysm and ICH were identified with median WFNS grade 5. Eleven patients were treated via primary, ultra-early DHC in mean 2.6 ± 1.4 hours after admission. Eight patients were treated via secondary DHC in 47.6 ± 34.2 hours after admission. In these patients, secondary DHC led to a significant decrease of peak ICP (50.2 mmHg preoperative vs. 10 mmHg postoperative). Mortality rate was six percent. In primary DHC group was a significantly better course of disease mirrored via reduced time of mechanical ventilation (14.4 ± 3.3 vs. 25.5 ± 3.4 days) and shorter hospital stay (18.7 ± 2.1 vs. 26.3 ± 3 days). Nevertheless there were no differences in long-term follow-up and most patients had a poor outcome. CONCLUSION: Our data demonstrate that DHC is feasible in aneurysmal ICH. Timing appears to be a crucial factor concerning early and long-term control of ICP and outcome. We are therefore in favor of ultra-early DHC to treat especially poor grade patients with intracerebral mass lesion in aneurysmal hemorrhage to facilitate the ICP management as well as care within the ICU.

Case report: a troublesome ophthalmic artery aneurysm.

Objective and Importance When treating large unruptured ophthalmic artery (OA) aneurysms causing progressive blindness, surgical clipping is still the preferred method because aneurysm sac decompression may relieve optic nerve compression. However, endovascular treatment of OA aneurysms has made important progress with the introduction of stents. Although this development is welcomed, it also makes the choice of treatment strategy less straightforward than in the past, with the potential of missteps. Clinical Presentation A 56-year-old woman presented with a long history of progressive unilateral visual loss and magnetic resonance imaging showing a 20-mm left-sided OA aneurysm. Intervention Because of her long history of very poor visual acuity, we considered her left eye to be irredeemable and opted for endovascular therapy. The OA aneurysms was treated with stent and coils but continued to grow, threatening the contralateral eye. Because she failed internal carotid artery (ICA) balloon test occlusion, we performed a high-flow extracranial-intracranial bypass with proximal ICA occlusion in the neck. However, aneurysm growth continued due to persistent circulation through reversed blood flow in distal ICA down to the OA and the cavernous portion of the ICA. Due to progressive loss of her right eye vision, we surgically occluded the ICA proximal to the posterior communicating artery and excised the coiled, now giant, OA aneurysm. This improved her right eye vision, but her left eye was permanently blind. Conclusion This case report illustrates complications of the endovascular and surgical treatment of a large unruptured OA aneurysm.

Antiangiogenic therapy inhibits the recruitment of vascular accessory cells to the perivascular niche in glioma angiogenesis.

OBJECTIVE: Antiangiogenic therapies could be limited by various escape mechanisms including bone marrow-derived myeloid cell-induced vasculogenesis. The recruitment of vascular accessory cells (VACs) to the tumor neovasculature is as a multistep process. However, the recruitment process of these cells during antiangiogenic treatment remains unknown. The aim of our study was to characterize the recruitment of VACs during antiangiogenic therapy using sunitinib. METHODS: C6 glioma cells were implanted into dorsal skinfold chambers. Animals received antiangiogenic therapy intraperitoneally for 5 days prior to VAC application intra-arterially. Intravital microscopy was performed during VAC injection and 1 and 48 h after injection. Analyses included total (TVD) and functional vessel densities (FVD), the perfusion index (PI), microvascular permeability, blood flow rate (Q), microvascular diameter (D), red blood cell velocity (RBCV), wall shear rate (γ), wall shear stress (τ), first and firm adhesions of VACs, and accumulation in the perivascular niche. RESULTS: Antiangiogenic therapy resulted in a significant reduction in TVD (365 ± 47 cm/cm(2) vs. 183 ± 37 cm/cm(2)) and FVD (227 ± 65 cm/cm(2) vs. 147 ± 25 cm/cm(2)) and an increase in PI, Q, D, and RBCV. γ and τ remained unaltered. Initial adhesion and firm adhesion were unaffected by antiangiogenic therapy; however, the accumulation in the perivascular niche was significantly diminished in treated tumors (53.7 ± 8% vs. 24.0 ± 17%). CONCLUSIONS: Antiangiogenic treatment inhibits the accumulation of VACs in the perivascular niche and therefore interferes with consecutive neovascularization.

Sacropelvic fixation versus fusion to the sacrum for spondylodesis in multilevel degenerative spine disease.

STUDY DESIGN: Retrospective study. OBJECTIVE: For successful multilevel correction and stabilization of degenerative spinal deformities, a rigid basal construct to the sacrum is indispensable. The primary objective of this study was to compare the results of two different sacropelvic fixation techniques to conventional stabilization to the sacrum in patients with multilevel degenerative spine disease. METHODS: A total of 69 patients with multisegmental fusion surgery (mean number of stabilized functional spinal units: 7.0 ± 3.3) with a minimum of 1-year follow-up were included. 32 patients received fixation to the sacrum (S1), 23 patients received S1 and iliac screw fixation (iliac) and 14 patients were treated with iliosacral plate fixation (plate). Primary outcome parameters were radiographic outcome concerning fusion in the segment L5-S1, rate of screw loosening, back and buttock pain reduction [numeric rating scale for pain evaluation: 0 indicating no pain, 10 indicating the worst pain], overall extent of disability after surgery (Oswestry Disability Index) and the number of complications. RESULTS: The three groups did not differ in body mass index, ASA score, the number of stabilized functional spinal units, duration of surgery, the number of previous spine surgeries, or postoperative complication rate. The incidence of L5-S1 pseudarthrosis after 1 year in the S1, iliac, and plate groups was 19, 0, and 29 %, respectively (p < 0.05 iliac vs. plate). The incidence of screw loosening after 1 year in the S1, iliac, and plate groups was 22, 4, and 43 %, respectively (p < 0.05 iliac vs. plate). Average Oswestry scores after 1 year in the S1, iliac, and plate groups were 40 ± 18, 42 ± 20, and 58 ± 18, respectively (p < 0.05 both S1 and iliac vs. plate). CONCLUSION: The surgical treatment of multilevel degenerative spine disease carries a significant risk for pseudarthrosis and screw loosening, mandating a rigid sacropelvic fixation. The use of an iliosacral plate resulted in an inferior surgical and clinical outcome when compared to iliac screws.

NDRG1 prognosticates the natural course of disease in WHO grade II glioma.

There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O (6) -methylguanine-DNA-methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.

Language mapping in healthy volunteers and brain tumor patients with a novel navigated TMS system: evidence of tumor-induced plasticity.

OBJECTIVE: This article explores the feasibility of a novel repetitive navigated transcranial magnetic stimulation (rnTMS) system and compares language mapping results obtained by rnTMS in healthy volunteers and brain tumor patients. METHODS: Fifteen right-handed healthy volunteers and 50 right-handed consecutive patients with left-sided gliomas were examined with a picture-naming task combined with time-locked rnTMS (5-10 Hz and 80-120% resting motor threshold) applied over both hemispheres. Induced errors were classified into four psycholinguistic types and assigned to their respective cortical areas according to the coil position during stimulation. RESULTS: In healthy volunteers, language disturbances were almost exclusively induced in the left hemisphere. In patients errors were more frequent and induced at a comparative rate over both hemispheres. Predominantly dysarthric errors were induced in volunteers, whereas semantic errors were most frequent in the patient group. CONCLUSION: The right hemisphere's increased sensitivity to rnTMS suggests reorganization in language representation in brain tumor patients. SIGNIFICANCE: rnTMS is a novel technology for exploring cortical language representation. This study proves the feasibility and safety of rnTMS in patients with brain tumor.

Combined temozolomide and sunitinib treatment leads to better tumour control but increased vascular resistance in O6-methylguanine methyltransferase-methylated gliomas.

INTRODUCTION: Combined antiangiogenic and cytotoxic treatment represents an appealing treatment approach for malignant glioma. In this study we characterised the antitumoural and microvascular consequences of sunitinib (Su) and temozolomide (TMZ) therapy and verified the ideal treatment protocol, with special focus on a potential therapeutic window for combined scheduling. MATERIALS AND METHODS: O(6)-Methylguanine methyltransferase (MGMT) status was analysed by pyrosequencing. Tumour growth of subcutaneous xenografts was assessed under different treatment protocols (TMZ, SU, SU followed by TMZ, TMZ followed by SU, combined TMZ/SU). Intravital microscopy (dorsal skinfold chamber model) assessed microvascular consequences. Immunohistochemistry included tumour and endothelial cell proliferation, apoptosis and vascular pericyte coverage. Real-time polymerase chain reaction (RT-PCR) analysed the expression of angiogenesis-related pathways in response to therapy. RESULTS: Combined TMZ/SU resulted in significantly reduced tumour growth compared to either monotreatment (TMZ: 106 ± 13 mm(3); SU: 114 ± 53 mm(3); TMZ/SU: 34 ± 7 mm(3)) by additional antiangiogenic effects and synergistic induction of apoptosis versus TMZ monotreatment. Sequential treatment protocols did not show additive antitumour responses. TMZ/SU aggravated vascular resistance mechanisms characterised by significantly higher blood flow rate (TMZ: 74 ± 34 µl/s; SU: 164 ± 36 µl/s; TMZ/SU: 254 ± 95 µl/s), reduced permeability (TMZ: 1.05 ± 0.02; SU: 0.99 ± 0.07; TMZ/SU: 0.89 ± 0.05) and recovery of pericyte-endothelial interactions (TMZ: 89 ± 7%; SU: 67 ± 9%, TMZ/SU:80 ± 10%) versus either monotreatment. Vascular resistance was paralleled by an increase in Ang-1 and Tie-2 and by the downregulation of Dll4. CONCLUSION: Sequential application of TMZ and SU in the angiogenic window does not add antitumour efficacy to monotherapy. Simultaneous application yields beneficial tumour control due to additive antiangiogenic and proapoptotic effects. Combined treatment may aggravate pericyte-mediated vascular resistance mechanisms by altering Ang-1-Tie-2 and Dll4/Notch pathways.

A new approach for corticospinal tract reconstruction based on navigated transcranial stimulation and standardized fractional anisotropy values.

PURPOSE: To establish a novel approach for fiber tracking based on navigated transcranial magnetic stimulation (nTMS) mapping of the primary motor cortex and to propose a new algorithm for determination of an individualized fractional anisotropy value for reliable and objective fiber tracking. METHODS: 50 patients (22 females, 28 males, median age 58 years (20-80)) with brain tumors compromising the primary motor cortex and the corticospinal tract underwent preoperative MR imaging and nTMS mapping. Stimulation spots evoking muscle potentials (MEP) closest to the tumor were imported into the fiber tracking software and set as seed points for tractography. Next the individual FA threshold, i.e. the highest FA value leading to visualization of tracts at a predefined minimum fiber length of 110 mm, was determined. Fiber tracking was then performed at a fractional anisotropy value of 75% and 50% of the individual FA threshold. In addition, fiber tracking according to the conventional knowledge-based approach was performed. Results of tractography of either method were presented to the surgeon for preoperative planning and integrated into the navigation system and its impact was rated using a questionnaire. RESULTS: Mapping of the motor cortex was successful in all patients. A fractional anisotropy threshold for corticospinal tract reconstruction could be obtained in every case. TMS-based results changed or modified surgical strategy in 23 of 50 patients (46%), whereas knowledge-based results would have changed surgical strategy in 11 of 50 patients (22%). Tractography results facilitated intraoperative orientation and electrical stimulation in 28 of 50 (56%) patients. Tracking at 75% of the individual FA thresholds was considered most beneficial by the respective surgeons. CONCLUSIONS: Fiber tracking based on nTMS by the proposed standardized algorithm represents an objective visualization method based on functional data and provides a valuable instrument for preoperative planning and intraoperative orientation and monitoring.