TERT promoter mutation and chromosome 6 loss define a high-risk subtype of ependymoma evolving from posterior fossa subependymoma.

Subependymomas are benign tumors characteristically encountered in the posterior fossa of adults that show distinct epigenetic profiles assigned to the molecular group "subependymoma, posterior fossa" (PFSE) of the recently established DNA methylation-based classification of central nervous system tumors. In contrast, most posterior fossa ependymomas exhibit a more aggressive biological behavior and are allocated to the molecular subgroups PFA or PFB. A subset of ependymomas shows epigenetic similarities with subependymomas, but the precise biology of these tumors and their potential relationships remain unknown. We therefore set out to characterize epigenetic traits, mutational profiles, and clinical outcomes of 50 posterior fossa ependymal tumors of the PFSE group. On histo-morphology, these tumors comprised 12 ependymomas, 14 subependymomas and 24 tumors with mixed ependymoma-subependymoma morphology. Mixed ependymoma-subependymoma tumors varied in their extent of ependymoma differentiation (2-95%) but consistently exhibited global epigenetic profiles of the PFSE group. Selective methylome analysis of microdissected tumor components revealed CpG signatures in mixed tumors that coalesce with their pure counterparts. Loss of chr6 (20/50 cases), as well as TERT mutations (21/50 cases), were frequent events enriched in tumors with pure ependymoma morphology (p < 0.001) and confined to areas with ependymoma differentiation in mixed tumors. Clinically, pure ependymoma phenotype, chr6 loss, and TERT mutations were associated with shorter progression-free survival (each p < 0.001). In conclusion, our results suggest that subependymomas may acquire genetic and epigenetic changes throughout tumor evolution giving rise to subclones with ependymoma morphology (resulting in mixed tumors) that eventually overpopulate the subependymoma component (pure PFSE ependymomas).

Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity.

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

Intradural spinal tumors in adults-update on management and outcome.

Among spinal tumors that occur intradurally, meningiomas, nerve sheath tumors, ependymomas, and astrocytomas are the most common. While a spinal MRI is the state of the art to diagnose intradural spinal tumors, in some cases CT scans, angiography, CSF analyses, and neurophysiological examination can be valuable. The management of these lesions depends not only on the histopathological diagnosis but also on the clinical presentation and the anatomical location, allowing either radical resection as with most extramedullary lesions or less invasive strategies as with intramedullary lesions. Although intramedullary lesions are rare and sometimes difficult to manage, well-planned treatment can achieve excellent outcome without treatment-related deficits. Technical advances in imaging, neuromonitoring, minimally invasive approaches, and radiotherapy have improved the outcome of intradural spinal tumors. However, the outcome in malignant intramedullary tumors remains poor. While surgery is the mainstay treatment for many of these lesions, radiation and chemotherapy are of growing importance in recurrent and multilocular disease. We reviewed the literature on this topic to provide an overview of spinal cord tumors, treatment strategies, and outcomes. Typical cases of extra- and intramedullary tumors are presented to illustrate management options and outcomes.

A Novel Type of IDH-wildtype Glioma Characterized by Gliomatosis Cerebri-like Growth Pattern, TERT Promoter Mutation, and Distinct Epigenetic Profile.

Diffuse gliomas in adults encompass a heterogenous group of central nervous system neoplasms. In recent years, extensive (epi-)genomic profiling has identified several glioma subgroups characterized by distinct molecular characteristics, most importantly IDH1/2 and histone H3 mutations. A group of 16 diffuse gliomas classified as "adult-type diffuse high-grade glioma, IDH-wildtype, subtype F (HGG-F)" was identified by the DKFZ v12.5 Brain Tumor Classifier . Histopathologic characterization, exome sequencing, and review of clinical data was performed in all cases. Based on unsupervised t -distributed stochastic neighbor embedding and clustering analysis of genome-wide DNA methylation data, HGG-F shows distinct epigenetic profiles separate from established central nervous system tumors. Exome sequencing demonstrated frequent TERT promoter (12/15 cases), PIK3R1 (11/16), and TP53 mutations (5/16). Radiologic characteristics were reminiscent of gliomatosis cerebri in 9/14 cases (64%). Histopathologically, most cases were classified as diffuse gliomas (7/16, 44%) or were suspicious for the infiltration zone of a diffuse glioma (5/16, 31%). None of the cases demonstrated microvascular proliferation or necrosis. Outcome of 14 patients with follow-up data was better compared to IDH-wildtype glioblastomas with a median progression-free survival of 58 months and overall survival of 74 months (both P <0.0001). Our series represents a novel type of adult-type diffuse glioma with distinct molecular and clinical features. Importantly, we provide evidence that TERT promoter mutations in diffuse gliomas without further morphologic or molecular signs of high-grade glioma should be interpreted in the context of the clinicoradiologic presentation as well as epigenetic profile and may not be suitable as a standalone marker for glioblastoma, IDH-wildtype.

Risk Factors for Dropping Out of Neurosurgical Residency Programs-A Survey Study.

BACKGROUND: Resident education has to adapt to a changing health care environment. Although aspects such as working hours and attrition rates have been studied in detail, data about the residents' perspective, especially in European countries, are underrepresented in the scientific literature. The aim of this study was to assess and report aspects of neurosurgical education in German-speaking countries and to identify risk factors for quitting or changing the neurosurgical residency program. METHODS: We conducted a nonanonymous online survey among neurosurgical residents in Germany, Austria, and Switzerland. Log-binomial regression models were calculated to further assess risk factors. RESULTS: Of 201 residents who responded to the survey, 37.3% (n = 75) dropped out of neurosurgical training programs, including 20 residents (10%) who ultimately quit neurosurgery and changed to another specialty. Only female gender (relative risk, 2.97; 95% confidence interval, 1.3-6.78) and starting residency in a city one studied or grew up in (2.38; 1.01-5.62) were significant risk factors. Residents who had close supervision at work (0.39; 0.17-0.89), who observed the residency program for >3 days before applying (0.54; 0.31-0.95), who had well-defined guidelines within the program (0.57; 0.35-0.92), and who were working in a university hospital (0.41; 0.26-0.64) were significantly less likely to quit or change their program. CONCLUSIONS: The high attrition rate, especially among female residents, in Germany, Austria, and Switzerland should encourage program directors to specifically address the issues reported by this survey during interviews and to further improve their residency program accordingly.

Posterior reversible encephalopathy syndrome mimicking cerebral metastasis: contraindication for biopsy.

The posterior reversible encephalopathy syndrome (PRES) is a well described entity of white matter pathology. PRES is triggered by numerous different factors such as acute elevated arterial hypertension, immunosupressive therapy, chemotherapy, etc. The case of a 67-year old woman is presented. The patient was treated for breast cancer 10 months ago and because of acute disorientation a magnetic resonance imaging (MRI) was performed. In the MRI biparieto-occipital hyperintense lesions were seen. Brain metastases were suspected. After chemotherapy and hypertonia and the typical appearance of the lesions in the MRI, PRES was also suspected. Before initializing the surgery for an open biopsy a follow-up MRI had been performed (2 weeks after initial MRI). In follow-up MRI the lesions disappeared completely proving the diagnosis of PRES. PRES can be misdiagnosed as a tumour and surgery could be mistakenly performed. It's important to keep the differential diagnosis of PRES in mind when radiologic features of the syndrome are present.

Syringomyelia regression after shunting of a trapped fourth ventricle.

We describe a case of progressive syringomyelia following post-infectious trapped fourth ventricle (TFV), which resolved after shunting of the fourth ventricle. A 28-year-old female who had previously undergone treatment of intracerebral hemorrhage and meningitis developed a hydrocephalus with TFV. After 3 years she developed disturbance of walking and coordination. Cranial-CT revealed an enlargement of the shunted fourth ventricle as a result of shunt dysfunction. Furthermore a cervical syringomyelia developed. The patient underwent a revision of a failed fourth ventriculo-peritoneal shunt. Postoperatively, syringomyelia resolved within 6 months and the associated neurological deficits improved significantly. An insufficiency of cerebrospinal fluid draining among patients with TFV can be associated with communicating syringomyelia. An early detection and treatment seems important on resolving syringomyelia and avoiding permanent neurological deficits. Ventriculo-peritoneal shunt in trapped fourth ventricles can resolve a secondary syringomyelia.

The Role of the Pterional Approach in the Surgical Treatment of Olfactory Groove Meningiomas: A 20-year Experience.

Background Olfactory groove meningiomas remain surgically challenging. The common microsurgical approaches suffer from late exposure of the neurovascular structures. Conversely, the pterional approach has the advantage of early dissection of the posterior neurovascular complex. Methods We reviewed the records of patients treated for olfactory groove meningioma in our department between 1991 and 2010. A total of 61 patients underwent removal of olfactory groove meningiomas via the pterional approach. These included 58 primary and 3 recurrent tumors. Mean overall follow-up time was 122 months. Results Early exposure and dissection of the internal carotid artery, middle cerebral artery, anterior cerebral artery, and optic nerve was feasible in all cases. Complete tumor removal was achieved in 60 patients. Morbidity and mortality rates were 26% and 1.6% respectively. Postoperative complications included epileptic seizures (five patients) and cerebrospinal fluid (CSF) leak (two patients). During follow-up, we recorded three tumor recurrences. Conclusions The pterional approach appears to be an excellent solution for the treatment of olfactory groove meningiomas. Its foremost advantage is early visualization of the posterior neurovascular complex. Moreover, it allows frontal sinus preservation and timely tumor devascularization and avoids excessive brain retraction. The pterional view is familiar to most neurosurgeons and therefore the transition to this technique is fairly straightforward.

Pediatric parafalcine empyemas.

Subdural intracranial empyemas and brain abscesses are a rare complication of bacterial sinusitis. Pediatric parafalcine abscesses are a rare entity with different treatment compared with other brain abscesses. We present two pediatric cases with falcine abscess as a sinusitis complication and introduce our department's treatment management. In addition a review of literature is performed. Surgical cases of our department and their management are compared with the current literature. In our cases, both of the children showed a recurrent empyema after the first surgical treatment and antibiotic therapy. A second surgical evacuation was necessary. The antibiotic therapy was given for 3 months. Short-time follow-up imaging is necessary irrespective of infection parameters in blood and patient's clinical condition. Especially in parafalcine abscesses a second look may be an option and surgical treatment with evacuation of pus is the treatment of choice if abscess remnants are visualized.