Through the orbit and beyond: Current state and future perspectives in endoscopic orbital surgery on behalf of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery. Research question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection. Material and methods: A PRISMA based literature search was performed to select the most relevant papers on the topic. Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery. Discussion and conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Case report: A vertebral bone spur as an etiology for spinal cord herniation: case presentation, surgical technique, and review of the literature.

Objective: The pathophysiology of idiopathic spinal cord herniation remains unknown. However, several different factors have been postulated, such as congenital causes (ventral dura mater duplication, preexisting pseudomeningocele, or other congenital dural defects), inflammation, remote spinal trauma, or thoracic disc herniation. Herein, the diagnosis and surgical treatment of a patient with spinal cord herniation caused by an intraspinal bone spur is presented along with a relevant literature review. Case presentation: A 56-year-old male patient presented with a non-traumatic Brown-Sequard syndrome persisting for over 1 year. A magnetic resonance imaging of the spinal axis revealed a ventral spinal cord displacement in the level of T 6/7. A supplementary thin-sliced computed tomography of the spine revealed a bone spur at the same level. For neurosurgical intervention, T 6 and T 7 laminectomy was performed. The cranial and caudal end of the right paramedian ventral dural defect was visualized and enlarged. Following extradural spinal cord mobilization by denticulate ligament transection, the spinal cord was finally released. The spinal cord was rotated and the ventral closure of the dural defect was performed by continuous suture. The patient recovered from surgery without additional deficits. The patient's postoperative gait, sensory, and motor function deficits improved, and further neurological deterioration was prevented. Conclusion: Since the first description of spinal cord herniation by Wortzman et al. in 1974, approximately 260 cases have been reported in the literature. In addition to other causes, intraspinal bone spur is a possible cause of spinal cord herniation.

Case report: Interdisciplinary treatment of complex C1/C2 fractures in a patient with concomitant three-vessel coronary artery disease requiring bypass surgery.

Background: Acute myocardial infarction (MI) frequently leads to consciousness disturbance following hemodynamic collapse. Therefore, MI can occur together with upper cervical spine trauma. Herein, we report the successful treatment of complex C1/C2 fractures in a patient with concomitant three-vessel coronary artery disease (CAD). Case presentation: A 70-year-old patient presented in our emergency outpatient clinic after a hemodynamic collapse without neurological deficits or heart-related complaints. Computed tomography (CT) scan of the cervical spine revealed a dislocated odontoid fracture Anderson and D'Alonzo type II and an unstable Gehweiler type III injury (Jefferson's fracture). An intradiploic arachnoid cyst in the posterior wall of the posterior fossa was a coincident radiological finding. Furthermore, coronary angiography confirmed three-vessel CAD with high-grade coronary artery stenosis. Indication for upper cervical spine surgery and bypass surgery was given. An interdisciplinary team of neurosurgeons, cardiothoracic surgeons and anesthesiologists evaluated the patient's case to develop the most suitable therapy concept and alternative strategies. Finally, in first step, C1-C2 fusion was performed by Harms technique under general anesthesia with x-ray guidance, spinal neuronavigation, Doppler ultrasound and cardiopulmonary monitoring. Cardiothoracic surgeons were on standby. One month later bypass surgery was performed uneventfully. Follow-up CT scan of cervical spine revealed intraosseous screw positioning and beginning fusion of the fractures. The patient did not develop neurological deficits and recovered completely from both surgeries. Conclusions: Treating complex C1/C2 fractures with concomitant severe CAD requiring treatment is challenging and carries a high risk of complications. To our knowledge, the literature does not provide any guidelines regarding therapy of this constellation. To receive upper cervical spine stability and to prevent both, spinal cord injury and cardiovascular complications, an individual approach is required. Interdisciplinary cooperation to determine optimal therapeutic algorithms is needed.

Surgical management of anterior clinoidal meningiomas: consensus statement on behalf of the EANS skull base section.

BACKGROUND: The optimal management of clinoidal meningiomas (CMs) continues to be debated. METHODS: We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of these tumors. The data from the literature along with contemporary practice patterns were discussed within the task force to generate consensual recommendations. RESULTS AND CONCLUSION: This article represents the consensus opinion of the task force regarding pre-operative evaluations, patient's counselling, surgical classification, and optimal surgical strategy. Although this analysis yielded only Class B evidence and expert opinions, it should guide practitioners in the management of patients with clinoidal meningiomas and might form the basis for future clinical trials.

Petroclival meningiomas: update of current treatment and consensus by the EANS skull base section.

BACKGROUND: The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. METHODS: A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. RESULTS: The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient's counselling. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the management of PCMs.

Surgical management of choroid plexus papilloma of the cerebellopontine and cerebellomedullary angle: classification and strategy.

Choroid plexus papillomas (CPPs) are primary neuroectodermal neoplasms that usually arise in the fourth ventricle in adults. In this study, we present 12 patients with CPP arising from the cerebellopontine angle (CPP-CPA) and/or of the cerebellomedullary angle (CPP-CMA) that were treated in our department. Patients who underwent surgery for the treatment for CPP-CPA/CMA from January 2004 to March 2020 were identified by a computer search of their files from the Department of Neurosurgery, Tübingen. CPPs were classified according to their location into type 1 (tumor portion only in the CPA,), type 2 (tumor portions only in the CMA), and type 3 (tumor portions both in the CPA and CMA). Patients were evaluated for initial symptoms, previous therapies in other hospitals, extent of tumor resection, recurrence rate, and complications by reviewing patient documents. Of approximately 1500 CPA lesions, which were surgically treated in our department in the last 16 years, 12 patients (mean age 42 ± 19 years) were found to have CPP-CPA/CMA. Five were male, and seven were female patients. Gross total resection was achieved in nine cases, and a subtotal resection was attained in three cases. Tumor recurrence in the same location after the first surgery in our hospital was observed in 2 patients after 15 and 40 months of follow-up, and in another patient, distant metastases (C3/4 and L3 levels) were observed. Surgical removal of CPP is the treatment of choice, but additional therapeutic options may be necessary in case of remnant tumor portions, recurrence, or malignant transformation.

Rapid motor cortical reorganization following subacute spinal cord dysfunction.

OBJECTIVE: Damage to the spinal cord is known to be associated with a posterior shift of the motor cortical upper limb representation, i.e. towards the somatosensory cortex. Due to missing pre-traumatic data, knowledge resulted from comparing findings between patients and healthy subjects. Here, we present a case of transient spinal cord injury resulting in a left-sided hemiparesis for 4 weeks. By chance, this patient had a pre-lesional navigated transcranial magnetic stimulation (nTMS) motor mapping 2 years before. Hence, nTMS mapping was repeated during the acute (after 1 day), sub-acute (after 10 days) and chronic (after 2 years) phase to trace the cortical reorganization following this incident. METHODS: Acute clinical work-up included magnetic resonance imaging and navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed with 110% of the abductor pollicis brevis muscle (APB) resting motor threshold (rMT). Amplitudes and latencies of the motor-evoked potential (MEPs) were recorded and analyzed. In addition, motor function was evaluated by the Medical Research Council (MRC) scale, a standard Purdue Pegboard test and by a reaction time (RT) task. RESULTS: MRI revealed no aberrant findings. nTMS mapping, however, showed a posterior shift of the APB representation from the anatomical hand knob towards the somatosensory cortex in the acute in comparison to the pre-lesional phase. Concomitantly, there was an increase of rMT (6%). Within 10 days, there was an incomplete reversal of the posterior shift in parallel with improvement of the clinical motor function. Long-term follow-up revealed a complete restitution of nTMS cortical mapping and motor function. CONCLUSION: The present case report thoroughly documents a rapid cortical reorganization within a few days after a transient spinal shock. Our data adds further evidence to the literature suggesting a posterior shift of motor cortical representation following spinal cord injury. For the first time, 52 cortical reorganization was shown idiosyncratically in a single patient arising from the fortuitous fact of having a pre - lesional nTMS map.

[Update on diagnostics and microsurgical treatment of vestibular schwannoma]. / Vestibularisschwannome ­ ein Update zu Krankheitsbild und mikrochirurgischer Behandlung.

Vestibular schwannomas are primary benign tumors of the cerebellopontine angle originating either from the superior or the inferior vestibular nerve. Hearing deterioration is the leading symptom, which is why the widespread name for this tumor is acoustic neuroma. Due to the widespread availability of magnetic resonance imaging (MRI), the diagnosis of vestibular schwannoma is frequently made in an early stage of the disease. In these cases a wait and scan policy is recommended. If the tumor grows, the therapeutic options are stereotactic radiotherapy or microsurgical tumor operation. Young patient age, functional hearing ability, persistent dizziness, cystic tumor consistence and large space-occupying tumor size are in favor of surgery via the retrosigmoid, transmeatal approach. In experienced hands excellent results in terms of functional preservation of the facial nerve and the cochlear nerve and radical tumor resection can be obtained.

Surgical management of collision-tumors between vestibular schwannoma and meningioma in the cerebellopontine angle in patients with neurofibromatosis type 2.

INTRODUCTION: When vestibular schwannoma (VS) collides with meningioma at the cerebellopontine angle (CPA), a particular threat occurs. Sudden acceleration of tumor growth and unpredictable involvement of cranial nerves results in a special environment that aggravates management. The goal of this study was to analyze the extent of resection, postoperative facial and cochlear function, surgical strategy, and survival rates in patients with neurofibromatosis type 2 (NF2) with meningioma-vestibular schwannoma (M-VS) collision tumors. METHODS: A total of 1284 VS, including 165 NF2 VS were operated at our department between January 2004 and May 2018. Out of these cases, a group of six NF2 patients with seven M-VS collision tumors was found following careful analysis of neuroradiological data and pathological and surgical reports. Patients were evaluated for extent of tumor resection and, furthermore, postoperative facial and hearing function. RESULTS: Six patients with NF2 with seven M-VS collision tumors were included in this study. Mean age was 32 ± 8.2 years. A gross total resection (GTR) of both colliding tumors was achieved in only one case, a GTR of the meningioma and a subtotal resection (STR) of the VS in four cases and in two cases only, the meningioma was removed. In five of the cases, facial function was intact or good (House and Brackmann grades I-II) at long-term follow-up (mean follow-up 22 months). No mortality occurred during follow-up. CONCLUSIONS: Collision between M and VS at the CPA is a particular phenomenon in NF2 patients that may aggravate the situation with less favorable surgical outcome than NF-2 VS without meningioma.

DNA methylation, transcriptome and genetic copy number signatures of diffuse cerebral WHO grade II/III gliomas resolve cancer heterogeneity and development.

BACKGROUND: Diffuse lower WHO grade II and III gliomas (LGG) are slowly progressing brain tumors, many of which eventually transform into a more aggressive type. LGG is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the heterogeneity of the DNA methylome, its function in tumor biology, coupling with the transcriptome and tumor microenvironment and its possible impact for tumor development. METHODS: We here present novel DNA methylation data of an LGG-cohort collected in the German Glioma Network containing about 85% isocitrate dehydrogenase (IDH) mutated tumors and performed a combined bioinformatics analysis using patient-matched genome and transcriptome data. RESULTS: Stratification of LGG based on gene expression and DNA-methylation provided four consensus subtypes. We characterized them in terms of genetic alterations, functional context, cellular composition, tumor microenvironment and their possible impact for treatment resistance and prognosis. Glioma with astrocytoma-resembling phenotypes constitute the largest fraction of nearly 60%. They revealed largest diversity and were divided into four expression and three methylation groups which only partly match each other thus reflecting largely decoupled expression and methylation patterns. We identified a novel G-protein coupled receptor and a cancer-related 'keratinization' methylation signature in in addition to the glioma-CpG island methylator phenotype (G-CIMP) signature. These different signatures overlap and combine in various ways giving rise to diverse methylation and expression patterns that shape the glioma phenotypes. The decrease of global methylation in astrocytoma-like LGG associates with higher WHO grade, age at diagnosis and inferior prognosis. We found analogies between astrocytoma-like LGG with grade IV IDH-wild type tumors regarding possible worsening of treatment resistance along a proneural-to-mesenchymal axis. Using gene signature-based inference we elucidated the impact of cellular composition of the tumors including immune cell bystanders such as macrophages. CONCLUSIONS: Genomic, epigenomic and transcriptomic factors act in concert but partly also in a decoupled fashion what underpins the need for integrative, multidimensional stratification of LGG by combining these data on gene and cellular levels to delineate mechanisms of gene (de-)regulation and to enable better patient stratification and individualization of treatment.

Depiction of the Superior Petrosal Vein Complex by 3D Contrast-Enhanced MR Angiography.

BACKGROUND AND PURPOSE: Intraoperative obliteration of the superior petrosal vein complex has a relevant risk of postoperative complications. A large venous diameter and the absence of anastomoses have been previously suggested as possible risk factors. 3D contrast-enhanced MRA was evaluated for the identification of superior petrosal vein anatomy. MATERIALS AND METHODS: Twenty-five patients (10 men; age, 20-77 years) with a 3D-MRA (voxel size, 0.4 × 0.4 × 0.5 mm3) at 3T, including the posterior fossa, were retrospectively identified. Image evaluation was performed independently by 2 neuroradiologists with respect to overall image quality and the presence, location, size, tributaries, and anastomotic veins of the superior petrosal vein complex. Additionally, 8 neurosurgical cases with intraoperative validation of the venous anatomy were examined. RESULTS: All studies were of diagnostic image quality. Interobserver agreement was excellent for image-quality measurements (r = 0.751-0.982) and good for measured vessel size (r = 0.563-0.828). A total of 83 superior petrosal veins were identified. The distribution of drainage locations and identification of tributaries and anastomotic veins were consistent with previous anatomic studies. The results showed that 4.8% of superior petrosal veins had a diameter of >2 mm and lacked a visible anastomosis. All surgical cases showed excellent agreement between the MRA and the intraoperative observations. CONCLUSIONS: 3D-MRA with high resolution is appropriate for analyzing the size, course, tributaries, and anastomoses of the superior petrosal vein. A total of 4.8% of the identified superior petrosal veins had to be classified as potential high-risk veins. The measurements correlated with the intraoperative findings.

Posterior fossa meningioma with invasion of the internal acoustic canal.

BACKGROUND: To evaluate the significance for outcome of meningioma invasion into the internal auditory canal (IAC) in posterior fossa meningiomas. METHODS: From April 2005 to September 2015, 174 posterior fossa meningiomas have been surgically treated in our Institution. Careful analysis of preoperative MRI depicted in 63 cases (36%) meningioma invasion into the IAC. A retrospective analysis was done of clinical and radiological presentation, surgical findings, outcome, and relevant prognostic factors in order to stratify the risk of complication and evaluate the surgical outcome. RESULTS: Gross total resection was achieved in 67% of patients. There was no mortality. CSF leak occurred in 5%. Postoperative moderately severe (HB 4) and severe dysfunction (HB 5) of the facial nerve was observed in 5% of patients. In 17 patients (27%), IAC was opened. Deterioration of facial function occurred in 24% of patients, hearing loss in 12%, and CSF leak in 6%. In 46 patients (73%), IAC was not opened. Deterioration of facial function occurred in 43% of patients, hearing loss in 13%, and CSF leak in 4%. Opening the IAC, a GTR was achieved in 82% while, without opening, in 61% of patients. CONCLUSIONS: Meningiomas of the posterior fossa may in one-third of the cases invade the IAC. Opening of the IAC in these cases was a crucial step for increasing the GTR. Despite the minimal increased risk of transient CSF leak, IAC opening was not associated with an increased risk of facial palsy or hearing loss in comparison to non-opening the IAC.

Foramen magnum meningioma: The midline suboccipital subtonsillar approach.

OBJECTIVES: Foramen magnum meningiomas (FMMs) represent a technical challenge even for experienced neurosurgeons, because they grow in close contact with osteoarticular, nervous, and vascular structures that cannot be sacrificed or retracted during surgery. Our goal is to present our experience with 24 cases of surgically resected foramen magnum meningiomas used the midline suboccipital subtonsillar approach and discussed the present risks associated with the treatment of this condition. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent surgery treatment for foramen magnum meningiomas operated on between August 2005 and July 2013. A total of 24 cases were included. Data regarding age, sex, symptoms and sign types, locations, surgical aspects, postoperative new deficits, and follow-up are presented. RESULTS: There were 18 female and 6 male patients (mean age: 52 years). The symptom among most patients (14 patients) was cervico-occipital pain, dysphagia and gait unsteadiness in five, and paresthesia of the upper limbs in four. Total removal of the tumor was achieved in 20 patients, subtotal in two, and partial resection in four patients. Two patients had permanent deficits. Follow-up was 45.6 months (range, 6 months to 8 years), there was no recurrence among tumors totally removed but 1 patient of regrowth among the cases with subtotal removal. CONCLUSIONS: Our experience confirmed that the midline suboccipital subtonsillar approach was accurate in safely removing anterior, anterolateral, and posterior FMMs. There was no significant postoperative complication in the remainder of the patientes, and their conditions improved after surgery.

Intraoperative MR Imaging in Neurosurgery.

Intraoperative magnetic resonance imaging (iMRI) has dramatically expanded and nowadays presents state-of-the-art technique for image-guided neurosurgery, facilitating critical precision and effective surgical treatment of various brain pathologies. Imaging hardware providing basic imaging sequences as well as advanced MRI can be seamlessly integrated into routine surgical environments, which continuously leads to emerging indications for iMRI-assisted surgery. Besides the obvious intraoperative diagnostic yield, the initial clinical benefits have to be confirmed by future-controlled long-term studies.

Maximizing the extent of resection and survival benefit of patients in glioblastoma surgery: high-field iMRI versus conventional and 5-ALA-assisted surgery.

AIMS: A safe total resection followed by adjuvant chemoradiotherapy should be the primary goal in the treatment of glioblastomas (GBMs) to enable patients the longest survival possible. 5-aminolevulinic acid (5-ALA)- and intraoperative MRI (iMRI)-assisted surgery, have been shown in prospective randomized trials to significantly improve the extent of resection (EOR) and subsequently survival of patients with GBMs. No direct comparison of surgical results between both techniques has been published to date. We analyzed the additional value of iMRI in glioblastoma surgery compared to conventional surgery with and without 5-ALA. METHODS: Residual tumor volumes, clinical parameters and 6-month progression-free survival (6M-PFS) rates after GBM resection were analyzed retrospectively for 117 patients after conventional, 5-ALA and iMRI-assisted surgery. RESULTS: Mean residual tumor volume (range) after iMRI-assisted surgery [0.5 (0.0-4.7) cm(3)] was significantly smaller compared to the residual tumor volume after 5-ALA-guided surgery [1.9 (0.0-13.2) cm(3); p = .022], which again was significantly smaller than in conventional white-light surgery [4.7 (0.0-30.6) cm(3); p = .007]. Total resections were significantly more common in iMRI- (74%) than in 5-ALA-assisted (46%, p = .05) or white-light surgery (13%, p = .03). Improvement of the EOR by using iMRI was safely achievable as peri- and postoperative morbidities were comparable between cohorts. Total resections increased 6M-PFS from 32% to 45%. CONCLUSIONS: Analysis of residual tumor volumes, total resections and neurological outcomes demonstrate that iMRI may be significantly superior to 5-ALA and white-light surgery for glioblastomas at comparable peri- and postoperative morbidities. Longer 6M-PFS was observed in patients with total resections.

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.

Long-term outcome prediction after a traumatic brain injury using early somatosensory and acoustic evoked potentials: analysis of the predictive value of the different single components of the potentials.

PURPOSE: The prediction of the long-term outcome of comatose patients after severe traumatic brain injury (TBI) using early somatosensory and acoustic evoked potentials is controversial. It was our aim to examine the different single components of the evoked potentials regarding their predictive capacity in comatose patients. METHODS: We examined the amplitude and latency of the wave N20, the amplitude differences between right and left hemisphere, the central conduction time (CCT), the amplitude ratio N20 left/N20 right, the amplitude and latency of peak V, the inter-peak latency I-V and the amplitude ratio V/I. The long-term clinical outcome of the patients was re-evaluated 3 years after their discharge and correlated with the different components. RESULTS: Only the central conduction time (CCT) and the latency of the wave N20 indicated a statistical correlation with the later outcome (p = 0.0366). The amplitude ratio of wave V/I of the EAEP did not reveal a significant statistical difference between the various outcome groups. CONCLUSIONS: In this study, the use of single components of the SSEP and EAEP per se could not predict the long-term clinical outcome after TBI. Combined systems such as the Riffel Score are necessary in order to achieve this goal.

Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy.

A distinct polyneuropathy (PNP) syndrome affects up to 66 % of patients with neurofibromatosis II (NF2). Whether this is primarily a diffuse PNP or due to single, surgically amenable mass lesions has not yet been conclusively demonstrated. We aimed to solve this question by investigating the pathomorphological MR imaging correlate of this rare disorder. Eight patients with NF2-PNP were characterized by clinical examination, electrophysiological studies, and genetic analysis. All patients additionally underwent extended peripheral nerve imaging by a novel protocol of large-coverage high-resolution MRI. Quantitative analyses were performed by separately evaluating cross-sectional images, and by categorizing lesions into non-compressive fascicular microlesions (<2 mm), intermediate lesions (2-5 mm), and compressive macrolesions (>5 mm). The predominant imaging findings were non-compressive fascicular microlesions and intermediate lesions. Proximal-to-distal cumulative lesion burden of these lesions correlated strongly with the severity of clinical symptoms of NF2-PNP. In contrast, compressive macrolesions were not found at all in several symptomatic extremities. We conclude that proximal-to-distal accumulation of non-compressive fascicular lesions instead of compressive mass lesions predominantly underlies the clinical manifestation and severity of NF2-associated PNP. Diagnostic management may now be assisted by large-coverage high-resolution imaging of plexus and peripheral nerves. Additionally, the results underscore the feasibility of this new method, which may open up new diagnostic and investigative possibilities for other disseminated disorders of the peripheral nervous system.