Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and <10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology.

Exploring Novel Therapeutic Opportunities for Glioblastoma Using Patient-Derived Cell Cultures.

Glioblastomas (GBM) are the most common, primary brain tumors in adults. Despite advances in neurosurgery and radio- and chemotherapy, the median survival of GBM patients is 15 months. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and molecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have established 13 GBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNA-seq, immunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1R132H, TP53 and PDGFRα), classical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), and the expression of pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, ß-Tubulin III) markers revealed the striking intertumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-CADHERIN and CD44 at the mRNA/protein levels suggested increased epithelial-to-mesenchymal transition (EMT) in most studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-derived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated cultures, the strongest accumulation of the apoptotic markers caspase 7 and PARP were found in WG4 cells with methylated MGMT, suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-derived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream signaling pathways. AG1478 caused decreased levels of phospho-STAT3, and thus inhibition of active STAT3 augmented antitumor effects of DOX and TMZ in cells with methylated and intermediate status of MGMT. Altogether, our findings show that GBM-derived cell cultures mimic the considerable tumor heterogeneity, and that identifying patient-specific signaling vulnerabilities can assist in overcoming therapy resistance, by providing personalized combinatorial treatment recommendations.

Preservation of the Hypoxic Transcriptome in Glioblastoma Patient-Derived Cell Lines Maintained at Lowered Oxygen Tension.

Despite numerous efforts aiming to characterise glioblastoma pathology (GBM) and discover new therapeutic strategies, GBM remains one of the most challenging tumours to treat. Here we propose the optimisation of in vitro culturing of GBM patient-derived cells, namely the establishment of GBM-derived cultures and their maintenance at oxygen tension mimicking oxygenation conditions occurring within the tumour. To globally analyse cell states, we performed the transcriptome analysis of GBM patient-derived cells kept as spheroids in serum-free conditions at the reduced oxygen tension (5% O2), cells cultured at atmospheric oxygen (20% O2), and parental tumour. Immune cells present in the tumour were depleted, resulting in the decreased expression of the immune system and inflammation-related genes. The expression of genes promoting cell proliferation and DNA repair was higher in GBM cell cultures when compared to the relevant tumour sample. However, lowering oxygen tension to 5% did not affect the proliferation rate and expression of cell cycle and DNA repair genes in GBM cell cultures. Culturing GBM cells at 5% oxygen was sufficient to increase the expression of specific stemness markers, particularly the PROM1 gene, without affecting neural cell differentiation markers. GBM spheroids cultured at 5% oxygen expressed higher levels of hypoxia-inducible genes, including those encoding glycolytic enzymes and pro-angiogenic factors. The genes up-regulated in cells cultured at 5% oxygen had higher expression in parental GBMs compared to that observed in 20% cell cultures, suggesting the preservation of the hypoxic component of GBM transcriptome at 5% oxygen and its loss in standard culture conditions. Evaluation of expression of those genes in The Cancer Genome Atlas dataset comprising samples of normal brain tissue, lower-grade gliomas and GBMs indicated the expression pattern of the indicated genes was specific for GBM. Moreover, GBM cells cultured at 5% oxygen were more resistant to temozolomide, the chemotherapeutic used in GBM therapy. The presented comparison of GBM cultures maintained at high and low oxygen tension together with analysis of tumour transcriptome indicates that lowering oxygen tension during cell culture may more allegedly reproduce tumour cell behaviour within GBM than standard culture conditions (e.g., atmospheric oxygen tension). Low oxygen culture conditions should be considered as a more appropriate model for further studies on glioblastoma pathology and therapy.

Freezing: how do water mites (Acari: Hydrachnidia) survive exposure to sub-zero temperatures?

Until now, very little is known about the ability of adult and deutonymph water mites (Acari, Hydrachnidia) to survive in sub-zero temperatures. Information concerns mainly water mites from vernal astatic waters, and the knowledge has never been experimentally verified. To determine the sensitivity of water mites to freezing, experiments were conducted on (1) the impact of acclimatization, (2) temperature, and (3) duration of freezing on survival, (4) the survival rate of water mites from various types of water bodies, and (5) the survival rate of water mites from different climatic zones. The experiments were carried out in a phytotron chamber, and water mites were placed in containers (10 × 10 × 5 cm) filled with 4/5 of water for 10 specimens each. Water mites were identified to the species level after finishing the experiments. The temperature was lowered 1 °C every hour until the target temperature was reached. After a certain period of freezing (depending on the treatment) the temperature was raised by 1 °C every hour until it reached 4 °C. The time of the experiment was measured from the moment the desired temperature was reached (below 0 °C) until the ice thawed and the temperature of 4 °C was reached again. The highest survival rates had Limnochares aquatica, Piona nodata, Sperchon clupeifer and Lebertia porosa, followed by L. insignis, Hygrobates longipalpis, H. setosus, Limnesia undulatoides, Piona pusilla, Arrenurus globator, Hydrodroma despiciens, Piona longipalpis, Sperchonopsis verrucosa, Unionicola crassipes and Mideopsis crassipes; no specimens of Torrenticola amplexa survived. The following conclusions were drawn: (1) water mites can survive freezing to -2 °C, lower temperatures are lethal for them; (2) they survived better the short period of freezing (24-48 h) than the long period (168 h); (3) resistance to freezing seems to be an evolutionary trait of individual species, only partly related to the living environment; and (4) freezing survival rates are linked to the region of Europe and are much lower in Southern than in Central Europe.

Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas.

Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.

Aberrantly Expressed RECQL4 Helicase Supports Proliferation and Drug Resistance of Human Glioma Cells and Glioma Stem Cells.

Anti-tumour therapies eliminate proliferating tumour cells by induction of DNA damage, but genomic aberrations or transcriptional deregulation may limit responses to therapy. Glioblastoma (GBM) is a malignant brain tumour, which recurs inevitably due to chemo- and radio-resistance. Human RecQ helicases participate in DNA repair, responses to DNA damage and replication stress. We explored if a helicase RECQL4 contributes to gliomagenesis and responses to chemotherapy. We found upregulated RECQL4 expression in GBMs associated with poor survival of GBM patients. Increased levels of nuclear and cytosolic RECQL4 proteins were detected in GBMs on tissue arrays and in six glioma cell lines. RECQL4 was detected both in cytoplasm and mitochondria by Western blotting and immunofluorescence. RECQL4 depletion in glioma cells with siRNAs and CRISPR/Cas9 did not affect basal cell viability, slightly impaired DNA replication, but induced profound transcriptomic changes and increased chemosensitivity of glioma cells. Sphere cultures originated from RECQL4-depleted cells had reduced sphere forming capacity, stronger responded to temozolomide upregulating cell cycle inhibitors and pro-apoptotic proteins. RECQL4 deficiency affected mitochondrial network and reduced mitochondrial membrane polarization in LN18 glioblastoma cells. We demonstrate that targeting RECQL4 overexpressed in glioblastoma could be a new strategy to sensitize glioma cells to chemotherapeutics.

Surgical Management of Intracranial Meningiomas in the Elderly: Early and Long-term Outcomes.

PURPOSE: In view of the risk associated with the surgical treatment of intracranial meningiomas in the elderly population due to the physiology of aging and multiple comorbidities, an attempt was made to identify factors influencing outcomes and to define the subgroup of patients who should not be operated on due to poor results. PATIENTS AND METHODS: A retrospective analysis of 58 patients over 70 years old with assessment of short-term and long-term outcomes. Scores by previously described CRGS, SKALE, and GSS grading systems were also calculated for our patients. RESULTS: Neurological morbidity was only associated with a critical location according to the SKALE grading system (P=0.02). Six patients (10.3%) died. Mortality was associated with the Karnofsky Performance Scale score (KPS ≤60 vs KPS ≥70; P=0.0162), the American Society of Anesthesiologists scale status (ASA 1 or 2 vs ASA 3; P=0.0022) and the WHO grade of meningiomas (P=0.012). Risk factors for tumor recurrence (six patients) were WHO grade (P=0.00048) and Simpson grade of resection (P=0.0437). At follow-up, excluding patients who died due to surgery or recurrence (15.5%), most patients improved (50%) or remained unchanged (25.9%) in relation to the preoperative KPS status. CONCLUSION: Postoperative neurological deterioration was only associated with a critical tumor location (skull base, eloquent area, large vessels involvement by the tumor). Due to a significantly higher risk of death, careful consideration should be taken for surgery in patients in a poor functional condition (KPS ≤60) or in a poor physical condition (ASA 3 status). An improvement or at least nonworsening of the neurological status in relation to the preoperative condition was observed in the majority of patients during follow-up.

Predictors of Class I epilepsy surgery outcome in tumour-related chronic temporal lobe epilepsy in adults.

OBJECTIVE: Temporal lobe tumours, especially low-grade gliomas and glioneuronal tumours, are common causes of seizures in patients referred for epilepsy surgery. We here present our experience of surgical treatment of patients with intractable chronic epilepsy associated with temporal lobe tumours, focusing on the long-term surgical outcomes and the features associated with better seizure control. METHODS: In this study, we retrospectively analysed 44 consecutive patients from a total of 182 with refractory temporal lobe epilepsy presenting with long-term intractable epilepsy due to a temporal lobe tumour who were surgically treated at our institution between 2005 and 2015 with post-surgical follow-up of at least two years. All patients underwent a standard pre-surgical evaluation that included: history and physical examination with a description of the seizure semiology, serial scalp EEG recording, brain MR imaging, and a detailed neuropsychological evaluation. Our surgical strategy comprised tumour resection, and combined mesial temporal and neocortical resection in most cases. RESULTS: No patient died during surgery or the postoperative course. Seven patients had postoperative complications, of whom two had permanent hemiparesis due to ischaemic stroke. At the final follow-up, a favourable seizure outcome (Engel Class I) was found in 37 patients (84%), including 31 (70.5%) in Engel Class IA (excellent result). Two (4.5%) patients presented with an Engel Class II outcome (unfavourable outcome). Five patients (11.5%) were in Engel Classes III or IV (surgical failure). We found that complete resection of the hippocampus along with tumour and temporal pole removal was strongly associated with seizure freedom (p = 0.015). Pathological diagnosis was also a significant prognostic indicator of tumour-related seizure freedom. Patients with a diagnosis of a glioneuronal tumour benefited from more seizure freedom after resection compared to those who had a low-grade glioma (p = 0.024). CONCLUSION: The most appropriate management of tumour-related chronic temporal lobe epilepsy in adults appears to be tai-lored temporal lobe resection including tumour and hippocampal complex removal. Surgical treatment of tumoural temporal lobe epilepsy demonstrates excellent results in terms of seizure improvement, especially in patients with glioneuronal tumours.

Trigone ventricular meningiomas - clinical characteristics, histopathology and results of surgical treatment.

AIM OF THE STUDY: Intraventricular meningiomas (IVMs) are rare tumours accounting for 0.5-3.0% of all meningiomas. IVMs require different surgical approaches and preparation in deep brain areas. The aim of our study was to present the clinico- -histopathological characteristics and treatment outcomes of trigone IVMs in a series of 15 patients. MATERIALS AND METHODS: Eight women and seven men (mean age 52) with 15 trigone IVMs were retrospectively analysed. Patients presented with headache (47%), psychoorganic syndrome (40%), hemianopsia (33%) or paresis (20%), including three (20%) patients with Karnofsky Performance Scale (KPS) < 80. Mean tumour size was 55.2 mm (range: 30-100 mm). RESULTS: Gross total tumour resection was performed in 14 (93%) cases, and subtotal in one (7%). A new deficit appeared in 83% (5/6) following a transparietal approach, in 14% (1/7) following a transtemporal approach, and in none of two patients following a transoccipital approach. Postoperative complications occurred in six (40%) patients; no patient died, but in two (13%) the new deficit was permanent. Tumour re-growth was found in two (13%) patients after 14 and 31 months. Meningiomas of WHO grade I occurred in 12, grade II in three, and grade III in one tumour recurrence. In long-term follow-up (mean: 60.8 months), including the results of revision operations, KPS: 80-100 was in 13 (87%) patients, KPS: 50 in one (severe hemiparesis after revision) and one patient was lost to follow-up (KPS: 100 on discharge). CONCLUSIONS: 20% of IVMs in our series were atypical. The results of surgery for IVMs, although satisfactory in general, require further improvement by reducing the rate of focal deficits resulting from a surgical approach.

Water mites (Acari, Hydrachnidia) of riparian springs in a small lowland river valley: what are the key factors for species distribution?

This paper examines the impact of disturbance factors-flooding and intermittency-on the distribution of water mites in the riparian springs situated in the valley of a small lowland river, the Krapiel. The landscape factors and physicochemical parameters of the water were analysed in order to gain an understanding of the pattern of water mite assemblages in the riparian springs. Three limnological types of springs were examined (helocrenes, limnocrenes and rheocrenes) along the whole course of the river and a total of 35 water mite species were found. Our study shows that flooding influences spring assemblages, causing a decrease in crenobiontic water mites in flooded springs. The impact of intermittency resulted in a high percentage of species typical of temporary water bodies. Surprisingly, the study revealed the positive impact of the anthropogenic transformation of the river valley: preventing the riparian springs from flooding enhances the diversity of crenobiontic species in non-flooded springs. In the conclusion, our study revealed that further conservation strategies for the protection of the riparian springs along large rivers would take into account ongoing climatic changes and possible the positive impact of the anthropogenic transformation of river valleys.

Surgical treatment for spinal dural arteriovenous fistulas: Outcome, complications and prognostic factors.

BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas (SDAVFs) are rare, acquired pathology and they inevitably lead to severe disability if untreated. The aim of this study is to present the outcome and complications, and to find factors that may affect the outcome after surgical treatment. METHODS: Seventeen consecutive patients (men - 14, women - 3, age: 41-79) were retrospectively analyzed. The patients presented with paraparesis (88%), bladder symptoms (71%) and/or sensory disturbances (65%). The fistula was found in the upper thoracic spine in 2 cases, in the lower thoracic (T7-Th12) in 11 cases, and in the lumbar spine in 4 cases. Microsurgical shunt interruption was performed in all, followed by epidural arteries coagulation in 12 cases. RESULTS: In the long term, improvement or achievement of a good stable condition was observed in 13 patients (76%), and no patient deteriorated. All 5 paraplegic patients improved by at least 1 grade in MCS. Satisfactory results (modified McCormick Scale grades I-II) were found in 10 patients (59%), and 15(88%) were independent. Postoperative complications occurred in 4 patients (24%), two of them (12%) required revision surgery for epidural hematoma. The success rate was 94%; one patient required revision surgery for recurrent SDAVF. Better neurological condition on admission (p=0.0098) and age >60 years (p=0.0498) were the factors associated with satisfactory outcome. CONCLUSIONS: Microsurgical closing of a SDAVF brings good and stable results over time. Aggressive treatment should be attempted even in cases of total loss of spinal cord function. Neurological condition before surgery and age may influence the outcome.

Diffusion tensor tractography of pyramidal tracts in patients with brainstem and intramedullary spinal cord tumors: Relationship with motor deficits and intraoperative MEP changes.

PURPOSE: To evaluate whether pyramidal tracts course alterations observed in diffusion tensor tractography (DTT) in cases of brainstem and intramedullary spinal cord tumors reflect patient clinical status and prognosis. MATERIALS AND METHODS: For this purpose, we assessed in 17 patients relationships between pyramidal tracts course alterations observed in DTT (classified into four categories: unaffected; displaced or interspaced; partially disintegrated and completely disintegrated) performed on a 1.5 Tesla scanner and the presence of preoperative motor deficits, changes observed in motor evoked potentials (MEPs) records at the beginning of the operation, deterioration of the MEPs records during the operation, and perioperative deterioration of muscle strength. RESULTS: We found that, if the picture of pyramidal tracts in DTT was worse, motor deficit was more common (P = 0.062). This observation was even more evident (P = 0.027), when cases with at least partially destroyed pyramidal tracts were compared with cases with normal or at most displaced or interspaced by tumor but still preserved pyramidal tracts. Significant relationships were also found between changes in DTT and abnormal MEP records at the beginning of the operation (P = 0.032) and perioperative deterioration of muscle strength (P = 0.0058). CONCLUSION: A close relationship was found between pyramidal tracts course alterations in DTT imaging and preoperative motor status and especially with changes in the MEP records at the beginning of the operation. DTT may be a method that allows the better planning of brainstem and intramedullary spinal cord tumors operations and may help in the risk assessment of postoperative motor deficits. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;46:715-723.

Midline lumbar fusion using cortical bone trajectory screws. Preliminary report.

INTRODUCTION: Midline lumbar fusion (MIDLF) using cortical bone trajectory is an alternative method of transpedicular spinal fusion for degenerative disease. The new entry points' location and screwdriving direction allow the approach-related morbidity to be reduced. AIM: To present our preliminary experience with the MIDLF technique on the first 5 patients with lumbar degenerative disease and with follow-up of at least 6 months. MATERIAL AND METHODS: Retrospective analysis was performed on the first 5 patients with foraminal (4) or central (1) stenosis operated on between December 2014 and February 2015. Three patients were fused at L4-L5 and two at the L5-S1 level. RESULTS: No intra- or post-operative complications occurred with this approach. An improvement regarding the leading symptom in the early postoperative period (sciatica 4/4, claudication 1/1) was achieved in all patients. The mean improvements in the visual analogue scale for low back and leg pain were 2.2 and 4.8 respectively. The mean Oswestry Disability Index scores were 52% (range: 16-82%) before surgery and 33% (range: 12-56%) at 3-month follow-up (mean improvement 19%). At the most recent follow-up, 4 patients reported the maintenance of the satisfactory result. The early standing and follow-up X-rays showed satisfactory screw placement in all patients. CONCLUSIONS: In our initial experience, the MIDLF technique seems to be an encouraging alternative to traditional transpedicular trajectory screws when short level lumbar fusion is needed. Nevertheless, longer observations on larger groups of patients are needed to reliably evaluate the safety of the method and the sustainability of the results.

Oblique corpectomy for treatment of cervical spine epidural abscesses: Report on four cases.

BACKGROUND: Spinal epidural abscesses (SEAs) in cervical locations are particularly life-threatening. Currently, SEAs are widely treated with bony decompression, followed by internal stabilization in purulent osteomyelitis. However, recently, a growing number of studies have reported minimally invasive approaches without internal fixation. PURPOSE: We describe four patients with cervical SEAs that were evacuated by oblique corpectomy (OC) without fusion. METHODS: This study included two women and two men (aged 44-90) that received operations for removing ventral cervical SEAs. All patients presented with progressively increasing myelopathy, and 3 had severe comorbid conditions. In all cases, a multilevel OC without fusion was performed. The amount of bone resection was tailored to fit the needs of granulation removal, with an effort to retain as much of the vertebral bodies as possible. Then, pus was evacuated and debridement of granulation was performed, followed by rinsing and drainage. RESULTS: The neurological status of 3 patients improved significantly after surgery. At the last follow-up examination, one showed full recovery, and in two a minor residual deficit persisted. During mean follow-up of 5.5 years, no internal stabilization was necessary. The oldest patient was tetraplegic, and had several concomitant diseases. That patient died from sudden cardiac arrest on the third postoperative day. Oblique corpectomy did not affect the anterior or posterior column. Additionally, it provided a broad view of the ventral aspect of the spinal canal. CONCLUSIONS: Oblique corpectomy allows appropriate spinal cord decompression and granulation removal in the case of cervical spine epidural abscess, without sacrificing spinal stability.

Epidermoid cysts of the cerebellopontine angle: Clinical features and treatment outcomes.

OBJECTIVE: To report clinical characteristics, treatment outcomes and risk of recurrence in patients with surgically treated cerebellopontine angle epidermoids. METHODS: In 1994-2013, we operated 17 patients, including 7 with tumor limited to the cerebellopontine angle, 7 with cerebellopontine angle tumor penetrating supratentorially, and 3 with cerebellopontine angle tumor extending along skull base to contralateral cerebellopontine angle. All patients were followed-up for the mean duration of 126 months. RESULTS: On admission cranial nerve symptoms predominated. Total tumor removal was achieved in 5 patients, and incomplete removal (with small tumor remnants left on vessels, nerves, or brainstem) in 12 patients. Postoperatively, preoperative deficits worsened in 2 and new postoperative deficits occurred in 10 patients. The extent of tumor expansion had no effect on postoperative morbidity and risk of recurrence. During long-term follow-up, improvement or resolution of preoperative deficits was seen in 11 of 17 patients, and new postoperative deficits in 8 of 10 patients. Symptomatic recurrences after an average of more than 9 years were noted in 5 patients, 3 of whom were reoperated. Recurrences occurred in some younger patients and always in area of primary tumor. No effect of extent of tumor removal on risk of recurrence was found. CONCLUSIONS: The extent of tumor removal had no effect on the risk of recurrence, and thus it may be acceptable to leave tumor capsule fragments adhering closely to nerves, vessels, or brainstem. During long-term follow-up, resolution or improvement of present preoperatively and new postoperative neurological deficits may be expected in most patients.

Surgery for sporadic vestibular schwannoma. Part II. Complications (not related to facial and auditory nerves).

INTRODUCTION: The aim of this study was to analyze the frequency and consequences of postoperative complications (PC) after surgery for sporadic vestibular schwannoma and to find factors that increase the risk of PC occurrence. MATERIALS AND METHODS: The study included 220 consecutive patients (134 women, 86 men; age ranged from 18 to 74) operated on with the retrosigmoid (217) or translabyrinthine (3) approach. Complicated postoperative period was defined as an occurrence of at least one of: cerebrospinal fluid (CSF) leakage, hematoma in the tumor bed, intracerebellar hematoma, cerebellar swelling, brainstem stroke, hydrocephalus (HCP), healing problems, meningitis and cranial nerves (excluding VII-VIII) palsies or cerebellar symptoms. Correlation studies and multivariate regression analysis were performed. RESULTS: PC occurred in 55 patients (25%). PC included lower cranial nerve (LCN) palsy (8.2%), cerebellar symptoms (7.3%), CSF leakage (5.9%), HCP (5%), CNVI palsy (3.1%), meningitis (1.8%), cerebellar swelling (1.4%), CNV dysfunction (0.9%), intracerebellar hematoma (0.5%) and lethal brainstem stroke (0.5%). In long term follow-up, LCN deficit was present in 2 patients (0.9%), cerebellar syndrome in 4(1.8%) and facial hypoesthesia in 2(0.9%). One patient (0.5%) developed bilateral blindness, secondary to preoperative optic nerve atrophy. As a result of PC, 10 patients (4.5%) required 11 additional surgical procedures. In statistical analysis, PC were independently related to preoperative cerebellar syndrome (p=0.002) and tumor size (>30 mm vs.<30 mm, p<0.05). The risk of PC diminished significantly with the increased number of performed procedures from 40% at the beginning to 16.4% in the last 55 cases. CONCLUSIONS: Tumor size, cerebellar syndrome at presentation and experience of the team were the three most important risk factors for PC occurrence. Permanent deficit secondary to PC remained in only 4% of the patients.

Surgery for sporadic vestibular schwannoma. Part I: General outcome and risk of tumor recurrence.

BACKGROUND: Vestibular schwannomas are slow growing, benign tumors. There are three possible management options: surgery, radiation treatment or active surveillance. The aim of this study was to assess the general outcome and risk of tumor recurrence. MATERIALS AND METHODS: The study included 220 consecutive patients (134 women, 86 men; the age ranged from 18 to 74) operated with the retrosigmoid transmeatal approach. The largest extrameatal diameter of the tumor ranged from 8 to 72mm (mean 30mm). According to the Samii grading scale, the tumors were classified as follows: T2-12 (6%), T3-51 (23%) and T4-157 (71%). Gross total resection was performed in 217 patients and neartotal in 3. RESULTS: Two hundred and eighteen (99.1%) patients were discharged home in a satisfactory neurological condition (GR or MD in GOS). One (0.5%) patient died due to brainstem infarction. One (0.5%) patient had unchanged severe cerebellar syndrome in comparison to the preoperative period (SD in GOS). In long-term follow-up, one patient went blind within a few months after surgery. Including the results of further neurosurgical procedures for CSF leak, shunt implantation, tumor regrowth and facial nerve reanimation, 98.6% of the patients were fully independent but with different neurological deficits. Tumor recurrence was observed in 5 (2.3%) patients during the follow-up period (mean term: 6.4 years). The average time to recurrence diagnosis was 8.8 years. All those patients were operated on again without any adjuvant therapy and there was no further re-growth at mean follow-up of 5.2 years. CONCLUSIONS: Complete removal of VS is usually curative and poses very low risks of severe disability (if audio-facial sequels are not included), mortality and long-term recurrence. For recurrent tumors, carefully tailored revision surgery without irradiation offers a high efficacy with low risk of complications.

Management of spinal tumors in neurofibromatosis type 2 patients.

OBJECTIVE: We sought to determine clinical characteristics of NF2 patients with spinal lesions and to define when and like the spinal tumors are a major problem in the treatment of patients with NF2. METHODS: The authors retrospectively reviewed the clinical records, neuroimaging studies, and follow-up data of the 34 patients with neurofibromatosis type 2, who were treated at our institution between 1998 and 2014. 23 patients harbored one or multiple spinal tumors. RESULTS: Patients with spinal tumors had a lower age at first symptoms of the disease, a higher number of intracranial meningiomas and non-vestibular schwannomas. 11 patients had one or more intramedullary tumors with MRI characteristics of spinal ependymomas. 22 patients had intradural extramedullary tumors. 7 patients presented with symptomatic spinal tumors on admission or developed symptoms during the follow-up. Only two intramedullary and four extramedullary tumors demonstrated growth in the mean radiological follow-up period of over 6 years. It was found that symptomatic both intra- and extramedullary tumors were associated with younger age at the onset of NF2-related symptoms. 2 patients with intramedullary tumors and 12 patients with extramedullary tumors underwent their tumors resection. In case of symptomatic tumors partial recovery was observed in two patients. CONCLUSION: It seems that close surveillance with MR imaging is a reasonable option for asymptomatic spinal tumors. Nevertheless, intramedullary tumor removal in non-growing and asymptomatic cases may be an option when ABI implantation is considered. Symptomatic tumors and those of documented growth should be eligible for surgical intervention.

Surgery for sporadic vestibular schwannoma. Part IV. Predictive factors influencing facial nerve function after surgery.

OBJECTIVE: To analyze the impact of various clinical, radiological and perioperative factors that could influence the facial nerve intraoperative disruption risk (CNVII-IDR) and its long-term function (CNVII-LTF) after vestibular schwannoma (VS) surgery. MATERIAL AND METHODS: The study included 212 patients operated on for sporadic VS with no history of previous treatment for VS or CNVII palsy. The mean size of the tumor was 30 mm. Gross (210) or near-total (2) resections were carried out using the retrosigmoid (210) or translabyrinthine (2) approach. Correlation studies and multivariate regression analysis (RA) were performed. RESULTS: In correlation studies, the CNVII-IDR was increased by: headaches and cerebellar ataxia if one of them was the first symptom of the tumor (33% and 29%, respectively, p=0.008); preoperative hydrocephalus (40% vs. 9%, p=0.01), tumor size >3 cm (18% vs. 5%, p<0.01), tumor volume >10 cm(3) (19% vs. 4%, p<0.01), right-sided location 15% vs. 6%, p=0.047), lateral "park-bench" position (19% vs. 5% for supine position, p<0.01) and the procedure order (16% for the first 106 procedures vs. 6% for the last 106 procedures, p<0.05). In RA the tumor volume (p=0.012), side of the tumor (p=0.028) and patient's position during surgery (p=0.016) independently affected the CNVII-IDR. The following factors correlated significantly with satisfactory CNVII-LTF (HB grades I-III): tumor stage