Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1.

Clear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors (n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis (n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group (n = 14) in comparison to those with meningioma WHO grade 2 (n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.

Brain invasion in meningiomas: does surgical sampling impact specimen characteristics and histology?

Brain invasion (BI) is a new criterion for atypia in meningiomas and therefore potentially impacts adjuvant treatment. However, it remains unclear whether surgical practice and specimen characteristics influence histopathological analyses and the accuracy of detecting BI. Tumor location, specimen characteristics, and rates of BI were compared in meningioma samples obtained from 2938 surgeries in different neurosurgical departments but diagnosed in a single neuropathological institute. Non-skull base tumor location was associated with CNS tissue on the microscopic slides (OR 1.45; p < .001), increasing specimen weight (OR 1.01; p < .001), and remaining tissue not subjected to neuropathological analyses (OR 2.18; p < .001) but not with BI (OR 1.29; p = .199). Specimen weight, rates of residual tissue not subjected to histopathological analyses, of BI and of brain tissue, on the microscopic slides differed among the neurosurgical centers (p < .001, each). Frequency of BI was increased in one department (OR 2.07; p = .002) and tended to be lower in another (OR .61; p = .088). The same centers displayed the highest and lowest rates of brain tissue in the specimen, respectively (p < .001). Moreover, the correlation of BI with the neurosurgical center was not confirmed when only analyzing specimen with evidence of brain tissue in microscopic analyses (p = .223). Detection of BI was not correlated with the intraoperative use of CUSA in subgroup analyses. Rates of brain invasion in neuropathological analyses are not associated with tumor location but differ among some neurosurgical centers. Evidence raises that surgical nuances impact specimen characteristics and therefore the accuracy of the detection of BI.

FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma.

Extraventricular neurocytoma (EVN) is a rare primary brain tumor occurring in brain parenchyma outside the ventricular system. Histopathological characteristics resemble those of central neurocytoma but exhibit a wider morphologic spectrum. Accurate diagnosis of these histologically heterogeneous tumors is often challenging because of the overlapping morphological features and the lack of defining molecular markers. Here, we explored the molecular landscape of 40 tumors diagnosed histologically as EVN by investigating copy number profiles and DNA methylation array data. DNA methylation profiles were compared with those of relevant differential diagnoses of EVN and with a broader spectrum of diverse brain tumor entities. Based on this, our tumor cohort segregated into different groups. While a large fraction (n = 22) formed a separate epigenetic group clearly distinct from established DNA methylation profiles of other entities, a subset (n = 14) of histologically diagnosed EVN grouped with clusters of other defined entities. Three cases formed a small group close to but separated from the epigenetically distinct EVN cases, and one sample clustered with non-neoplastic brain tissue. Four additional samples originally diagnosed otherwise were found to molecularly resemble EVN. Thus, our results highlight a distinct DNA methylation pattern for the majority of tumors diagnosed as EVN, but also indicate that approximately one third of morphological diagnoses of EVN epigenetically correspond to other brain tumor entities. Copy number analysis and confirmation through RNA sequencing revealed FGFR1-TACC1 fusion as a distinctive, recurrent feature within the EVN methylation group (60%), in addition to a small number of other FGFR rearrangements (13%). In conclusion, our data demonstrate a specific epigenetic signature of EVN suitable for characterization of these tumors as a molecularly distinct entity, and reveal a high frequency of potentially druggable FGFR pathway activation in this tumor group.

Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis.

The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.

Cerebral amyloidoma is characterized by B-cell clonality and a stable clinical course.

Amyloidomas are rare amyloid-containing lesions, which may also occur in the central nervous system. Etiology, pathogenesis and clinical course are poorly understood. To gain more insight into the biology of cerebral amyloidoma, they aimed to characterize its histopathological, molecular and clinical features in a retrospective series of seven patients. FFPE tissue specimens were examined using immunohistochemistry, chromogenic in situ hybridization (CISH) for light chains kappa and lambda as well as an IgH gene clonality analysis. Follow-up information was gathered by reviewing patient records and imaging results. Median age of the three males and four females was 50 years (range: 35-53 years). All cerebral amyloidomas were located supratentorially and were classified as lambda light chain amyloidosis (AL-λ; n = 6) and kappa light chain amyloidosis (AL-κ; n = 1) on immunohistochemistry and CISH. B-cell clonality was confirmed by IgH gene clonality assay in all cases examined. After a median follow-up of 21 months, all patients were alive and showed stable disease. No progression to systemic disease was observed. In conclusion, their data suggest that cerebral amyloidoma is a local disease characterized by B-cell clonality and associated with a stable clinical course.

Prospective analysis of neuropsychological deficits following resection of benign skull base meningiomas.

OBJECTIVE Resection of skull base tumors is challenging. The introduction of alternative treatment options, such as radiotherapy, has sparked discussion regarding outcome in terms of quality of life and neuropsychological deficits. So far, however, no prospective data are available on this topic. METHODS A total of 58 patients with skull base meningiomas who underwent surgery for the first time were enrolled in this prospective single-center trial. The average age of the patients was 56.4 ± 12.5 years. Seventy-nine percent of the tumors were located within the anterior skull base. Neurological examinations and neuropsychological testing were performed at 3 time points: 1 day prior to surgery (T1), 3-5 months after surgery (T2), and 9-12 months after surgery (T3). The average follow-up duration was 13.8 months. Neuropsychological assessment consisted of quality of life, depression and anxiety, verbal learning and memory, cognitive speed, attention and concentration, figural memory, and visual-motor speed. RESULTS Following surgery, 23% of patients showed transient neurological deficits and 12% showed permanent new neurological deficits with varying grades of manifestation. Postoperative quality of life, however, remained stable and was slightly improved at follow-up examinations at T3 (60.6 ± 21.5 vs 63.6 ± 24.1 points), and there was no observed effect on anxiety and depression. Long-term verbal memory, working memory, and executive functioning were slightly affected within the first months following surgery and appeared to be the most vulnerable to impairment by the tumor or the resection but were stable or improved in the majority of patients at long-term follow-up examinations after 1 year. CONCLUSIONS This report describes the first prospective study of neuropsychological outcomes following resection of skull base meningiomas and, as such, contributes to a better understanding of postoperative impairment in these patients. Despite deterioration in a minority of patients on subscales of the measures used, the majority demonstrated stable or improved outcome at follow-up assessments.

Prechiasmatic transection of the optic nerve in optic nerve glioma: technical description and surgical outcome.

Optic pathway glioma (OPG) encompasses a spectrum of findings ranging from lesions confined to the optic nerve only, lesions affecting the optic chiasm and hypothalamus, and lesions with diffuse involvement of a large part of the optic pathway and neighboring structures. The majority of pediatric low-grade astrocytomas in the optic/chiasmatic region are typical pilocytic astrocytoma. The rest of them (10 %) may be other gliomas such as fibrillary pilomyxoid astrocytoma (grade 2 WHO). The postsurgical local recurrence rate of 55 to 76 % has been reported in some histological subtypes such as pilomyxoid astrocytoma (grade 2). Performing a prechiasmatic transection might offer a new surgical option to avoid further tumor growth toward the chiasm in the optic nerve glioma with predominantly orbital manifestations. In this retrospective study, four patients (three children, two without neurofibromatosis type 1 (NF1), and one with NF1 and one adult without NF1) with optic nerve glioma without involvement of the chiasm but blindness, disfiguring proptosis, and pain of the affected eye were included. The surgical approach was performed as a combined approach from pterional extradural and intradural. Without any exceptions, vision of the contralateral eye could be preserved and did not show any deterioration after surgery or during the follow-up time between 17 and 106 months. Furthermore, in all patients, gross total tumor resection could be achieved. During follow-up observation in all patients, no further tumor progress or recurrences could be observed. None of the patients were treated postoperatively by radiotherapy or chemotherapy. Prechiasmatic transection of the optic nerve in optic nerve glioma without affecting the chiasm might offer a surgical treatment option to control tumor growth and to preserve vision of the contralateral eye.

Pathological Location of Cranial Nerves in Petroclival Lesions: How to Avoid Their Injury during Anterior Petrosal Approach.

Objectives Numerous surgical approaches have been developed to access the petroclival region. The Kawase approach, through the middle fossa, is a well-described option for addressing cranial base lesions of the petroclival region. Our aim was to gather data about the variation of cranial nerve locations in diverse petroclival pathologies and clarify the most common pathologic variations confirmed during the anterior petrosal approach. Method A retrospective analysis was made of both videos and operative and histologic records of 40 petroclival tumors from January 2009 to September 2013 in which the Kawase approach was used. The anatomical variations of cranial nerves IV-VI related to the tumor were divided into several location categories: superior lateral (SL), inferior lateral (IL), superior medial (SM), inferior medial (IM), and encased (E). These data were then analyzed taking into consideration pathologic subgroups of meningioma, epidermoid, and schwannoma. Results In 41% of meningiomas, the trigeminal nerve is encased by the tumor. In 38% of the meningiomas, the trigeminal nerve is in the SL part of the tumor, and it is in 20% of the IL portion of the tumor. In 38% of the meningiomas, the trochlear nerve is encased by the tumor. The abducens nerve is not always visible (35%). The pathologic nerve pattern differs from that of meningiomas for epidermoid and trigeminal schwannomas. Conclusion The pattern of cranial nerves IV-VI is linked to the type of petroclival tumor. In a meningioma, tumor origin (cavernous, upper clival, tentorial, and petrous apex) is the most important predictor of the location of cranial nerves IV-VI. Classification of four subtypes of petroclival meningiomas using magnetic resonance imaging is very useful to predict the location of deviated cranial nerves IV-VI intraoperatively.

Anterior petrosal approach: The safety of Kawase triangle as an anatomical landmark for anterior petrosectomy in petroclival meningiomas.

OBJECT: Anterior petrosectomy through the middle fossa is a well-described option for addressing cranial base lesions of the petroclival region. To access posterior fossa through middle fossa, we quantitatively evaluate the safety of Kawase triangle as an anatomical landmark. METHOD: We reviewed pre- and postoperative Multi-Slice CT scan (1mm thickness) of patients with petroclival meningioma between Jan 2009 and Sep 2013 in which anterior petrosectomy was performed to access the posterior fossa part of the tumor. The distances between drilling start and finish edge to the vital anatomical skull base structures such as internal auditory canal (IAC) and superior semicircular canal and petrous apex (petrous part of the carotid artery) were measured and analyzed. RESULTS: Drilling entrance length is directly related with tumor size. The distances between anatomical structures and drilling points decrease with increasing tumor size, but it always remains a safe margin between drilling points and IAC, internal carotid artery (ICA), and semicircular canals in axial and coronal views. CONCLUSION: The Kawase triangle is shown to be a safe anatomical landmark for anterior petrosectomy. The described landmarks avoid damage to the vital anatomical structures during access to the posterior fossa through middle fossa, despite temporal bone anatomical variations and different tumor sizes.

Multi-size, Multi-angle Microbipolar Forceps for Skull Base Surgery: Technical Note.

Objective Hemorrhage control in skull base surgery is critical but hindered by the lack of instruments suitable for coagulating structural curves and corners. The main impediment is that most of the instruments currently used are right-angled and unsuitable because anatomical and pathologic structures are three-dimensional objects having complex curves and corners. In this article, we present a solution: the use of angled bipolar microforceps having a range of small diameters and angles for dissection and coagulation. Methods Utilizing modern design software and up-to-date synthetic and metallic materials, a variety of nonstick bipolar microforceps with different angles and very fine tips (0.2-1.2 mm) were designed and constructed for use on different anatomical and pathologic curves. The tips of the forceps were made very fine to improve coagulation precision as well as to improve microdissection dexterity. The blades were made long and thin to improve visibility during coagulation and dissection procedures. As a result, these multi-size, multiangle micro instruments can be used not only for coagulation but also for microdissection or tumor removal in most anatomical areas accessed during the course of skull base surgery Results The research, design, and construction of a new bipolar microforceps with different angles and sizes represents a technical innovation that can lead to improved surgical outcomes. Conclusion The new micro-instruments enhance the quality and quantity of tumor and tissue resection and dissection in skull base surgery and open the possibility of new surgical approaches to microscopic tumor resection and hemorrhage coagulation in the anatomical areas of the skull base.

Disabling vertigo and tinnitus caused by intrameatal compression of the anterior inferior cerebellar artery on the vestibulocochlear nerve: a case report, surgical considerations, and review of the literature.

Microvascular compression of the vestibulocochlear nerve is known as a cause of tinnitus and vertigo in the literature, but our review of the literature shows that the compression is usually located in the cerebellopontine angle and not intrameatal. We present a case of intrameatal compression of the anterior inferior cerebellar artery (AICA) on the vestibulocochlear nerve of a 40-year-old woman with symptoms of disabling vertigo and intermittent high-frequency tinnitus on the left side without any hearing loss for ∼ 4 years. Magnetic resonance imaging of the brain did not show any abnormality, but magnetic resonance angiography showed a left intrameatal AICA loop as a possible cause of the disabling symptoms. After the exclusion of other possible reasons for disabling vertigo, surgery was indicated. The intraoperative findings proved the radiologic findings. The large AICA loop was found extending into the internal auditory canal and compressing the vestibulocochlear nerve. The AICA loop was mobilized and separated from the vestibulocochlear nerve. The patient's symptoms resolved immediately after surgery, and no symptoms were noted during 2 years of follow-up in our clinic. Her hearing was not affected by the surgery. In addition to other common reasons, such as acoustic neuroma, disabling vertigo and tinnitus can occur from an intrameatal arterial loop compression of the vestibulocochlear nerve and may be treated successfully by drilling the internal acoustic meatus and separating the arterial conflict from the vestibulocochlear nerve.

Sacral dural arteriovenous fistula presented as an acute isolated thoracic myelopathy: clinical and surgical importance.

UNLABELLED: We report a case of dural Arteriovenous Fistula (AVF) supplied by the lateral sacral artery that is located in the sacral region and presented as isolated thoracic myelopathy. METHOD AND RESULTS: After S3 hemilaminectomy and opening the dura, the engorged arterialized vein has been interrupted. Postoperatively, the patient's symptoms and myelopathy gradually resolved. CONCLUSION: We are going to highlight the clinical and surgical importance of our case and discuss the pathophysiology of such an unusual clinical finding.

"Münster correlation" in temporal bone: surgical relevance of an anatomical study.

Resection of the temporal bone to various degrees provides different levels of access to lesions of the posterior fossa. However, precise distances to the petrosal bone are still not clearly described. We evaluated the different distances of temporal bone landmarks in order to assess their variations and the possible correlations between them. We also evaluated the surgical relevance of the possible correlations. An anatomical study was performed on 60 temporal bones from 60 human cadavers. All bones contained an adequate portion of the petrous apex and attached fossa dura. We analyzed the variation in different distances between landmarks and also the correlations between different measured distances. There was a statistically significant correlation between the distance between the inferior axial plane of the posterior semicircular canal to the superior plane of jugular bulb and the thickness of the mastoid cortex at the M point (M point was defined by the authors). This correlation is important for estimating the height of the jugular bulb during a lateral suboccipital craniotomy in cerebellopontine angle surgery. The Münster correlation is an easy and safe method for estimating the height of the jugular bulb in cerebellopontine angle surgery.

Pre-chiasmatic transection of the optic nerve can save contralateral vision in patients with optic nerve sheath meningioms.

OBJECTIVES: With respect to its characteristic pattern of growth from the orbit into the intracranial space toward the chiasm, patients with optic nerve sheath meningiomas (ONSM) are threatened to loose function of both optic nerves. Fortunately, in less than 5% both optic nerves are involved initially. Hence, prevention of vision of the contralateral eye is the foremost aim of any therapy. Performing pre-chiasmatic transection might offer a further treatment option to avoid further tumor growth toward the chiasm. PATIENTS AND METHODS: In this retrospective study 12 patients with ONSM and blindness of the affected eye were included. The surgical approach was performed either from pterional intradural or as a combined approach from pterional extra- and intradural. RESULTS: Without any exceptions, vision of the contralateral eye could be preserved and did not show any deterioration after surgery or during the follow-up time of 50.6 months. Furthermore in 58.3% of patients gross total tumor resection could be achieved. During follow up observation in 67% of patients no further tumor progress or recurrences could be observed. 4 patients, however, showed delayed tumor progress or recurrences that were treated by radiotherapy. CONCLUSION: Pre-chiasmatic transection of the optic nerve might offer a surgical treatment option to control tumor growth and to preserve vision of the contralateral eye.

Isolated primary craniopharyngioma in the cerebellopontine angle.

Between January 2000 and January 2011, we diagnosed three patients with isolated craniopharyngioma in the cerebellopontine angle (CPA). Brain MRI revealed cystic lesions with various imaging characteristics, including hypointensity on T1-weighted (T1W) images and hyperintensity on T2-weighted (T2W) images. The first patient's lesion showed rim enhancement after gadolinium administration. The second patient's lesion showed mixed signal intensity on both T1W and T2W images. The third patient's MRI showed a well-defined cystic lesion in the right CPA that compressed the brainstem. This lesion was hyperintense on T1W images and hypointense relative to cerebrospinal fluid on T2W images, and was peripherally enhanced after gadolinium administration. All three patients underwent surgical intervention through a suboccipital retrosigmoid craniotomy/craniectomy and lesions that did not adhere to adjacent tissues were removed completely. Histopathological examination confirmed the tumors to be adamantinomatous craniopharyngioma. The post-operative course was uneventful for all patients uneventful and no tumor recurrences were detected at the last follow-up. Primary CPA craniopharyngioma can be completely removed surgically, provided it does not densely adhere to vital structures.

Helmet use in winter sport activities--attitude and opinion of neurosurgeons and non-traumatic-brain-injury-educated persons.

PURPOSE: During the last winter season, some fatal sport injuries with severe traumatic brain injury (TBI) prompted major discussions about protective helmet use. Although ski helmets reportedly lead to a 60% decrease of risk to incur TBI, little is known about the distribution of helmet users and which factors are crucial for the decision to wear a helmet. Especially, it is unknown whether knowledge or experience concerning TBI in winter sports influences the use of helmets, as well as the attitude and opinion of people. METHODS: Since treatment of TBI is a major field in neurosurgery, 55 neurosurgical departments (NS) in Germany, Switzerland and Austria were addressed and asked to answer anonymous questionnaires. A "non-trauma-educated" control cohort (NTP) was interviewed in ski resorts in Austria as well as sports equipment stores in Germany. RESULTS: Questionnaires were returned by 465 NS and 546 NTP. Half of NS and NTP wore helmets in winter sports. Although some interviewees showed cognitive dissonant behaviour, experience in TBI after ski or snowboard accidents significantly affected the decision to wear helmets. After the fatal ski accidents, and increased media coverage 15.4% NS and 13.2% NTP bought their helmet. Furthermore, incidence of helmet use in children was correlated with the actual use and disposition of their parents to make the use of helmet compulsory. CONCLUSIONS: This study indicates that brain-trauma education affects ones attitude and opinion concerning protective helmet use in winter sports. However, without neglecting educational measures, emotional arguments should be added in the promotion of helmets to make them a popular integral part of winter sport outfits.