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Kinins are a set of peptides present in tissues that are involved in the inflammatory response and cancer progression. However, studies showing the expression of kinin receptors in human glioma samples are still incomplete and contradictory. The aim of the present study was to ascertain the expression of BDKRB1 and BDKRB2 genes, as well as the level of B1R and B2R proteins in human gliomas, depending on the degree of malignancy. Additionally, representative kinin-dependent genes with altered expression were indicated. The expression profile of kinin-dependent genes was determined using oligonucleotide microarray technique. In addition, RT-qPCR was used to assess the expression level of selected differentiating genes. The location of kinin receptors in brain gliomas was assessed using immunohistochemical methods. The oligonucleotide microarray method was used to identify 12 mRNA IDs of kinin-related genes whose expression was upregulated or downregulated in gliomas of different grades. In immunohistochemically stained samples, the concentrations of BR1 and BR2 proteins, measured by optical density, were statistically significantly higher in grade G3 vs. G2 and G4 vs. G3. Increased expression of kinin receptors BDKRB1 and BDKRB2 in brain gliomas, depending on the degree of malignancy, suggests the involvement of kinins and their receptors in the disease's pathogenesis. Quantitative assessment of mRNA BDKRB1 , PRKAR1A , MAP2K , and EGFR in patients with brain tumors may hold diagnostic and therapeutic significance.

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., (© 2023 UICC.)

There is no established method to assess the PD-L1 expression in brain tumours. Therefore, we investigated the suitability of affibody molecule (Z PD-L1 ) radiolabelled with F-18 (Al 18 F) and Ga-68 to measure the expression of PD-L1 in xenograft mouse models of GBM. Mice bearing subcutaneous and orthotopic tumours were imaged 1 h post-radioconjugate administration. Ex vivo biodistribution studies and immunohistochemistry (IHC) staining were performed. Tumoural PD-L1 expression and CD4+/CD8+ tumour-infiltrating lymphocytes were evaluated in human GBM specimens. Z PD-L1 was radiolabelled with radiochemical yields of 32.2 ± 4.4% (F-18) and 73.3 ± 1.8% (Ga-68). The cell-associated radioactivity in vitro was consistent with PD-L1 expression levels assessed with flow cytometry. In vivo imaging demonstrated that 18 F-AlF-NOTA-Z PD-L1 can distinguish between PD-L1 high-expressing tumours (U87-MGvIII) and PD-L1-negative ones (H292 PD-L1Ko ). The radioconjugate was quickly cleared from the blood and normal tissues, allowing for high-contrast images of brain tumours as early as 1 h post-injection. 68 Ga-NOTA-Z PD-L1 showed heterogeneous and diffuse accumulation that corresponded to the extensively infiltrating GCGR-E55 tumours involving contiguous lobes of the brain. Lastly, 39% of analysed GBM patient samples showed PD-L1+ staining of tumour cells that was associated with elevated levels of CD4+ and CD8+ lymphocytes. Our results suggest that the investigated radioconjugates are very promising agents with the potential to facilitate the future design of treatment regimens for GBM patients.

Background: Although electroencephalography (EEG)-based indices may show artifactual values, raw EEG signal is seldom used to monitor the depth of volatile induction of general anesthesia (VIGA). The current analysis aimed to identify whether bispectral index (BIS) variations reliably reflect the actual depth of general anesthesia during presence of different types of epileptiform patterns (EPs) in EEGs during induction of general anesthesia., Methods: Sixty patients receiving either VIGA with sevoflurane using increasing concentrations (group VIMA) or vital capacity (group VCRII) technique or intravenous single dose of propofol (group PROP) were included. Monitoring included facial electromyography (fEMG), fraction of inspired sevoflurane (FiAA), fraction of expired sevoflurane (FeAA), minimal alveolar concentration (MAC) of sevoflurane, BIS, standard EEG, and hemodynamic parameters., Results: In the PROP group no EPs were observed. During different stages of VIGA with sevoflurane in the VIMA and VCRII groups, presence of polyspikes and rhythmic polyspikes in patients' EEGs resulted in artifactual BIS values indicating a false awareness/wakefulness from anesthesia, despite no concomitant change of FiAA, FeAA, and MAC of sevoflurane. Periodic epileptiform discharges did not result in aberrant BIS values., Conclusion: Our results suggest that raw EEG correlate it with values of BIS, FiAA, FeAA, and MAC of sevoflurane during VIGA. It seems that because artifactual BIS values indicating false awareness/wakefulness as a result of presence of polyspikes and rhythmic polyspikes in patients' EEGs may be misleading to an anesthesiologist, leading to unintentional administration of toxic concentration of sevoflurane in ventilation gas.

Objective: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients., Methods: The authors retrospectively analyzed the medical records of symptomatic patients with CM-I who underwent posterior fossa decompression between 2010 and 2018 in six neurosurgical departments. Each patient was clinically assessed at the latest available follow-up. Gestalt outcome was determined as improved, unchanged, or worsened compared with the preoperative clinical state. Additionally, the CCOS score was calculated for each patient based on the detailed clinical data. To verify the ability of the CCOS to determine clinical improvement, the area under the receiver operating characteristic (AUROC) curve was evaluated. A logistic regression analysis using all four components of the CCOS (pain symptoms, nonpain symptoms, functionality, and complications) was performed to establish predictors of the improved outcome., Results: Seventy-five individuals with a mean age of 42 ± 15.32 years were included in the study. The mean follow-up duration was 52 ± 33.83 months. Considering gestalt outcome evaluation, 41 patients (54.7%) were classified as improved, 24 (32%) as unchanged, and 10 (13.3%) as worsened. All patients with a CCOS score of 14 or higher improved, while all those with a CCOS score of 8 or lower worsened. The AUROC was 0.986, suggesting almost perfect accuracy of the CCOS in delineating clinical improvement. A CCOS score of 13 showed high sensitivity (0.93) and specificity (0.97) for identifying patients with clinical improvement. Additionally, a meaningful correlation was found between higher CCOS scores in each component and better outcomes. Patient stratification by total CCOS score showed that those categorized as improved, unchanged, and worsened scored prevalently between 13 and 16 points, 10 and 12 points, and 4 and 9 points, respectively., Conclusions: In this adult cohort, the CCOS was found to be almost perfectly accurate in reflecting postoperative clinical improvement. Moreover, all four CCOS components (pain symptoms, nonpain symptoms, functionality, and complications) significantly correlated with patient clinical outcomes.

Intracranial aneurysms (IAs) are persistent, localised dilatations of the arterial wall that are found in approximately 3% of the general population. The most severe complication of IAs is rupture, which results in devastating consequences such as subarachnoid haemorrhage and brain damage with serious neurological sequelae. Numerous studies have characterised the mechanisms underlying IA development and growth and identified a number of environmental modifiable (smoking, hypertension) and nonmodifiable risk factors (related to the histology of cerebral arteries and genetic factors) in its pathogenesis. Haemodynamic stress also likely plays a crucial role in the formation of IAs and is conditioned by the geometry and morphology of the vessel tree, but its role in the natural history of unruptured IAs remains poorly understood; it is believed that changes in blood flow might generate the haemodynamic forces that are responsible for damage to the vascular wall and vessel remodelling that lead to IA formation. This review summarises the most relevant data on the current theories on the formation of IAs, with particular emphasis on the roles of special conditions resulting from the microscopic anatomy of intracranial arteries, haemodynamic factors, bifurcation morphometry, inflammatory pathways, and the genetic factors involved in IA formation., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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% O 2 ), cells cultured at atmospheric oxygen (20% O 2 ), 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., Competing Interests: The authors declare no conflict of interest.

Malignant gliomas are the most frequent primary brain tumors in adults. They are genetically heterogenous and invariably recur due to incomplete surgery and therapy resistance. Circulating tumor DNA (ctDNA) is a component of circulating cell-free DNA (ccfDNA) and represents genetic material that originates from the primary tumor or metastasis. Brain tumors are frequently located in the eloquent brain regions, which makes biopsy difficult or impossible due to severe postoperative complications. The analysis of ccfDNA from a patient's blood presents a plausible and noninvasive alternative. In this study, freshly frozen tumors and corresponding blood samples were collected from 84 brain tumor patients and analyzed by targeted next-generation sequencing (NGS). The cohort included 80 glioma patients, 2 metastatic cancer patients, and 2 primary CNS lymphoma (PCNSL) patients. We compared the pattern of genetic alterations in the tumor DNA (tDNA) with that of ccfDNA. The implemented technical improvements in quality control and library preparation allowed for the detection of ctDNA in 8 out of 84 patients, including 5 out of 80 glioma patients. In 32 out of 84 patients, we found potentially pathogenic genetic alterations in ccfDNA that were not detectable in tDNA. While sequencing ccfDNA from plasma has a low efficacy as a diagnostic tool for glioma patients, we concluded that further improvements in sample processing and library preparation can make liquid biopsy a valuable diagnostic tool for glioma patients.

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system tumour in adults. It has extremely poor prognosis since the current standard of care, comprising of gross total resection and temozolomide (TMZ) chemoradiotherapy, prolongs survival, but does not provide a durable response. To a certain extent, this is due to GBM's heterogeneous, hostile and cold tumour microenvironment (TME) and the unique ability of GBM to overcome the host's immune responses. Therefore, there is an urgent need to develop more effective therapeutic approaches. This review provides critical insights from completed and ongoing clinical studies investigating novel immunotherapy strategies for GBM patients, ranging from the use of immune checkpoint inhibitors in different settings of GBM treatment to novel combinatorial therapies. In particular, we discuss how treatment regimens based on single antigen peptide vaccines evolved into fully personalised, polyvalent cell-based vaccines, CAR-T cell, and viral or gene therapies. Furthermore, the results of the most influential clinical trials and a selection of innovative preclinical studies aimed at activating the immunologically cold GBM microenvironment are reviewed., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 Niedbała et al.)

Genes associated with the TGFβ isoforms are involved in a number of different cancers, and their effect on the progression of brain tumors is also being discussed. Using an oligonucleotide microarray method, we assessed differences in expression patterns of genes in astrocytic brain tumor sections from 43 patients at different stages of disease. Quantitative mRNA assessment of the three TGFβ isoforms was also performed by real-time RT-qPCR. Oligonucleotide microarray data were analyzed using the PL-Grid Infrastructure. The microarray analysis showed a statistically significant (p < 0.05) increase in TGFβ1 and TGFβ2 expression in G3/G4 stage relative to G2, whereas real-time RT-qPCR validation confirmed this change only for the TGFβ2 isoform (p < 0.05). The oligonucleotide microarray method allowed the identification of 16 differential genes associated with TGFβ isoforms. Analysis of the STRING database showed that the proteins encoded by the analyzed genes form a strong interaction network (p < 0.001), and a significant number of proteins are involved in carcinogenesis. Differences in expression patterns of transcripts associated with TGFβ isoforms confirm that they play a role in astrocytic brain tumor transformation. Quantitative assessment of TGFβ2 mRNA may be a valuable method to complement the diagnostic process in the future.

Background: Surgical resection followed by chemo-radiation postpones glioblastoma (GBM) progression and extends patient survival, but these tumours eventually recur. Multimodal treatment plans combining intraoperative techniques that maximise tumour excision with therapies aiming to remodel the immunologically cold GBM microenvironment could improve patients' outcomes. Herein, we report that targeted photoimmunotherapy (PIT) not only helps to define tumour location and margins but additionally promotes activation of anti-GBM T cell response., Methods: EGFR-specific affibody molecule (Z EGFR:03115 ) was conjugated to IR700. The response to Z EGFR:03115 -IR700-PIT was investigated in vitro and in vivo in GBM cell lines and xenograft model. To determine the tumour-specific immune response post-PIT, a syngeneic GBM model was used., Results: In vitro findings confirmed the ability of Z EGFR:03115 -IR700 to produce reactive oxygen species upon light irradiation. Z EGFR:03115 -IR700-PIT promoted immunogenic cell death that triggered the release of damage-associated molecular patterns (DAMPs) (calreticulin, ATP, HSP70/90, and HMGB1) into the medium, leading to dendritic cell maturation. In vivo, therapeutic response to light-activated conjugate was observed in brain tumours as early as 1 h post-irradiation. Staining of the brain sections showed reduced cell proliferation, tumour necrosis, and microhaemorrhage within PIT-treated tumours that corroborated MRI T 2 *w acquisitions. Additionally, enhanced immunological response post-PIT resulted in the attraction and activation of T cells in mice bearing murine GBM brain tumours., Conclusions: Our data underline the potential of Z EGFR:03115 -IR700 to accurately visualise EGFR-positive brain tumours and to destroy tumour cells post-conjugate irradiation turning an immunosuppressive tumour environment into an immune-vulnerable one., (© 2021. The Author(s).)

Background: Previously published computational fluid dynamics (CFD) studies regarding intracranial aneurysm (IA) formation present conflicting results. Our study analysed the involvement of the combination of high wall shear stress (WSS) and a positive WSS gradient (WSSG) in IA formation., Methods: We designed a case-control study with a selection of 38 patients with an unruptured middle cerebral artery (MCA) aneurysm and 39 non-aneurysmal controls to determine the involvement of WSS, oscillatory shear index (OSI), the WSSG and its absolute value (absWSSG) in aneurysm formation based on patient-specific CFD simulations using velocity profiles obtained from transcranial colour-coded sonography., Results: Among the analysed parameters, only the WSSG had significantly higher values compared to the controls (11.05 vs - 14.76 [Pa/mm], P = 0.020). The WSS, absWSSG and OSI values were not significantly different between the analysed groups. Logistic regression analysis identified WSS and WSSG as significant co-predictors for MCA aneurysm formation, but only the WSSG turned out to be a significant independent prognosticator (OR: 1.009; 95% CI: 1.001-1.017; P = 0.025). Significantly more patients (23/38) in the case group had haemodynamic regions of high WSS combined with a positive WSSG near the bifurcation apex, while in the control group, high WSS was usually accompanied by a negative WSSG (14/39). From the analysis of the ROC curve for WSSG, the area under the curve (AUC) was 0.654, with the optimal cut-off value -0.37 Pa/mm. The largest AUC was recognised for combined WSS and WSSG (AUC = 0.671). Our data confirmed that aneurysms tend to form near the bifurcation apices in regions of high WSS values accompanied by positive WSSG., Conclusions: The development of IAs is determined by an independent effect of haemodynamic factors. High WSS impacts MCA aneurysm formation, while a positive WSSG mainly promotes this process., (© 2021. The Author(s).)

High-grade gliomas (HGGs), the most common and aggressive primary brain tumors in adults, inevitably recur due to incomplete surgery or resistance to therapy. Intratumoral genomic and cellular heterogeneity of HGGs contributes to therapeutic resistance, recurrence, and poor clinical outcomes. Transcriptomic profiles of HGGs at recurrence have not been investigated in detail. Using targeted sequencing of cancer-related genes and transcriptomics, we identified single nucleotide variations, small insertions and deletions, copy number aberrations (CNAs), as well as gene expression changes and pathway deregulation in 16 pairs of primary and recurrent HGGs. Most of the somatic mutations identified in primary HGGs were not detected after relapse, suggesting a subclone substitution during the tumor progression. We found a novel frameshift insertion in the ZNF384 gene which may contribute to extracellular matrix remodeling. An inverse correlation of focal CNAs in EGFR and PTEN genes was detected. Transcriptomic analysis revealed downregulation of genes involved in messenger RNA splicing, cell cycle, and DNA repair, while genes related to interferon signaling and phosphatidylinositol (PI) metabolism are upregulated in secondary HGGs when compared to primary HGGs. In silico analysis of the tumor microenvironment identified M2 macrophages and immature dendritic cells as enriched in recurrent HGGs, suggesting a prominent immunosuppressive signature. Accumulation of those cells in recurrent HGGs was validated by immunostaining. Our findings point to a substantial transcriptomic deregulation and a pronounced infiltration of immature dendritic cells in recurrent HGG, which may impact the effectiveness of frontline immunotherapies in the GBM management. KEY MESSAGES: Most of the somatic mutations identified in primary HGGs were not detected after relapse. Focal CNAs in EGFR and PTEN genes are inversely correlated in primary and recurrent HGGs. Transcriptomic changes and distinct immune-related signatures characterize HGG recurrence. Recurrent HGGs are characterized by a prominent infiltration of immature dendritic and M2 macrophages.

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.

Background and Objectives: Raw electroencephalographic (EEG) signals are rarely used to monitor the depth of volatile induction of general anaesthesia (VIGA) with sevoflurane, even though EEG-based indices may show aberrant values. We aimed to identify whether response (RE) and state entropy (SE) variations reliably reflect the actual depth of general anaesthesia in the presence of different types of epileptiform patterns (EPs) in EEGs during induction of general anaesthesia., Materials and Methods: A randomized, prospective clinical study was performed with 60 patients receiving VIGA using sevoflurane with the increasing concentrations (group VIMA) or the vital capacity (group VCRII) technique or an intravenous single dose of propofol (group PROP). Facial electromyography (fEMG), fraction of inspired sevoflurane (FiAA), fraction of expired sevoflurane (FeAA), minimal alveolar concentration (MAC) of sevoflurane, RE and SE, and standard electroencephalographic evaluations were performed in these patients., Results: In contrast to periodic epileptiform discharges, erroneous SE and RE values in the patients' EEGs were associated with the presence of polyspikes (PS) and rhythmic polyspikes (PSR), which were more likely to indicate toxic depth rather than false emergence from anaesthesia with no changes in the FiAA, FeAA, and MAC of sevoflurane., Conclusion: Calculated RE and SE values may be misleading during VIGA when EPs are present in patients' EEGs. During VIGA with sevoflurane, we recommend monitoring raw EEG data in scientific studies to correlate it with potentially erroneous RE and SE values and the end-tidal concentration of sevoflurane in everyday clinical practice, when monitoring raw EEG is not available, because they can mislead anaesthesiologists to reduce sevoflurane levels in the ventilation gas and result in unintentional true emergence from anaesthesia. Further studies are required to investigate the behaviour of EEG-based indices during rapid changes in sevoflurane concentrations at different stages of VIGA and the influence of polyspikes and rhythmic polyspikes on the transformation of EEG signals into a digital form., Competing Interests: The authors declare no conflict of interest.

Purpose: Severe postoperative pain (SPP) may occur after lumbar discectomy. To prevent SPP and reduce rescue opioid consumption, infiltration anaesthesia (IA) has been combined with general anaesthesia (GA). This study verified how GA combined with IA facilitated intra- and postoperative demand for opioids and affected the incidence of SPP in patients subjected to open lumbar discectomy., Materials/methods: Ninety-nine patients undergoing lumbar discectomy under GA with Surgical Pleth Index (SPI)-guided fentanyl (FNT) administration were randomly assigned to receive IA combined with either 0.2% bupivacaine (BPV) or 0.2% ropivacaine (RPV) with FNT 50 μg and compared with controls (BF, RF, and C groups, respectively)., Results: Ninety-four patients were included in the final analysis. Adjusted according to SPI, total intraoperative FNT dosages did not differ between the study groups (p = 0.23). The proportion of patients who reported SPP was the highest in group C (41.9%) than in the RF (12.9%) and BF groups (31.3%) (p < 0.05). Mild pain was experienced by 67.7%, 53.1% and 32.3% of patients from the RF, BF and C groups, respectively (p < 0.01). Morphine requirement was the highest in the control group (7.1 ± 5.9 mg), followed by the RF (2.7 ± 5.3 mg) and BF groups (4 ± 4.9 mg) (p < 0.05)., Conclusions: IA using RPV/FNT mixture significantly reduced SPP and postoperative demand for morphine in patients subjected to lumbar discectomy under GA., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

This study analyzed morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal middle cerebral artery (MCA) bifurcations and their relationship with optimal values derived from the principle of minimum work (PMW). The study included 96 patients with MCA aneurysm and 94 controls. Aneurysm patients presented with significantly higher values of the radius and cross-sectional area of the MCA trunk, angle between the post-bifurcation branches (α angle) and volume flow rate (VFR) and had significantly lower values of junction exponent and pulsatility index than the controls. The Φ 1 and Φ 2 angles (angles between the MCA trunk axis and the larger and smaller branch, respectively) and α angle in all groups were significantly larger than the optimal PMW-derived angles. The most important independent predictors of MCA aneurysm were junction exponent (odds ratio, OR = 0.42), α angle (OR = 1.07) and VFR (OR = 2.36). Development of cerebral aneurysms might be an independent effect of abnormalities in hemodynamic and morphometric factors. The risk of aneurysm increased proportionally to the deviation of morphometric parameters of the bifurcation from their optimal PMW-derived values. The role of bifurcation angle in aneurysm development needs to be explained in future research as the values of this parameter in both aneurysm patients and non-aneurysmal controls in were scattered considerably around the PMW-derived optimum.

Objective: The aim of the study was to establish the usefulness of various neuropsychological tests in patients undergoing surgery due to low-grade glioma (LGG) involving supplementary motor area (SMA)., Patients and Methods: 21 patients diagnosed with LGG involving the SMA underwent, before and after surgery, screening tests (Mini Mental State Examination - MMSE, Montreal Cognitive Assessment - MoCA and Frontal Assessment Battery - FAB), tests to assess language functions (Addenbrook's Cognitive Examination-III - ACE-III, phonetic fluency tests and semantic fluency tests), tests to assess memory functions (Rey's 15-word test - RAVLT and Diagnostic Test for Brain Damage by Hillers- DCS), tests to assess executive functions (Wisconsin Card Sorting Test - WCST, Ruff Figural Fluency Test - RFFT and Trail Making Test)., Results: Before surgery, in the screening tests the patients obtained below normal scores in the MoCA test only. After surgery, the scores of such tests were significantly worse than the scores before surgery, while the MMSE test scores continued to be within the normal range. In phonetic and semantic fluency tests, the patients obtained worse scores, both before and after surgery. The differences in the test scores between the two periods, i.e. before and after surgery, were statistically significant. Although the patients obtained worse scores both before and after surgery in the ACE III test, the differences in the test scores were not statistically significant. The scores obtained in all tests assessing the executive and memory functions before and after surgery were within the normal range. The scores in such tests (except the WCCT) dropped significantly after surgery., Conclusions: Patients diagnosed with LGG involving the SMA reveal the impairment of cognitive functions, in particular language functions. After surgery, a significant impairment of all elementary cognitive functions, such as attention, memory, language and executive functions and complex cognitive functions, occurs. The most sensitive tests to detect cognitive disorders, executive dysfunctions and speech disturbances in patients undergoing surgery due to glioma include the MoCA, FAB and Phonetic and Semantic Fluency Tests., (Copyright © 2018. Published by Elsevier B.V.)

Glioblastomas (GBMs) are high-grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR-specific affibody (Z EGFR:03115 ) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near-infrared light produces a cytotoxic response. Z EGFR:03115 -IR700DX EGFR-specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter-Glo® assay, and in vivo using subcutaneous U87-MGvIII xenografts. In addition, mice were imaged pre- and post-PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor-dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the Z EGFR:03115 -IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof-of-concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts., (© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The aim of this study was to verify whether L-lactide/DL-lactide copolymer 80/20 (PLDLLA) and platelet-rich plasma (PRP) trigger bone formation within critical-sized calvarial defects in adult sheep ( n = 6). Two craniectomies, each ca. 3 cm in diameter, were created in each animal. The first craniectomy was protected with an inner polylactide membrane, filled with PRP-polylactide granules, and covered with outer polylactide membrane. The second control craniectomy was left untreated. The animals were euthanized at 6, 7, 17, 19, 33, and 34 weeks after surgery, and the quality and the rate of reossification were assessed histomorphometrically and microtomographically. The study demonstrated that application of implants made of PLDLLA 80/20 combined with an osteopromotive substance (e.g., PRP) may promote bone healing in large calvarial defect in sheep. These promising proof-of-concept studies need to be verified in the future on a larger cohort of animals and over a longer period of time in order to draw definitive conclusions.

Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3-5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated. Some of them, such as IDH mutations, 1p19q deletion, MGMT promoter methylation, and EGFRvIII amplification are frequently tested in routine clinical practice. With the development of sequencing technology, detailed characterization of GBM molecular signatures has facilitated a more personalized therapeutic approach and contributed to the development of a new generation of anti-GBM therapies such as molecular inhibitors targeting growth factor receptors, vaccines, antibody-based drug conjugates, and more recently inhibitors blocking the immune checkpoints. In this article, we review the exciting progress towards elucidating the potential of current and novel GBM biomarkers and discuss their implications for clinical practice., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor that might occur in nasal cavity and paranasal sinuses. It is characteristic for poor prognosis, especially the solid histopathological subtype of the tumor. ACC might spread along nerves and fascias and it is usually diagnosed at advanced stage. Computed tomography and magnetic resonance imaging together with fine-needle biopsy are the gold standards in the diagnostic procedure of the cancer. Surgery with adjuvant therapy are the most common methods of treatment. Among the surgical approaches, the functional endonasal sinus surgery seems to be the most appropriate and favorable way of treatment. In the study, the authors present a case of a 62-year-old patient with T4aN0M0 ACC tumor treated endoscopically at the Department of Laryngology and ENT Oncology, WSS No. 5 in Sosnowiec. The authors indicate the usefulness of FESS procedure in the treatment of malignancies of nasal cavity and paranasal sinuses. They also review the recent publications on endonasal versus open approach in similar cases. In conclusions, the authors favor endonasal approach as a mini-invasive method of surgical treatment of ACC of paranasal sinuses that results in satisfactory oncological outcome and high quality of patient's life.

Purpose: We analyzed the usefulness and prognostic value of intraoperative monitoring for identification of the oculomotor (III) and the abducens (VI) nerve in patients with cavernous sinus meningiomas., Material/methods: 43 patients diagnosed with cavernous sinus meningiomas were divided according to their topography. Function of the nerves was scored on original clinical and neurophysiological scales., Results: The percentage of nerves identified correctly with the monitoring was significantly higher (91% vs. 53% for nerve III and 70% vs. 23% for nerve VI, p<0.001). The fractions of nerves III and VI identified correctly by means of the monitoring were significantly higher in the case of tumors with intra- and extracavernous location (89% vs. 32%, p<0.01) and intracavernous tumors (80% vs. 20%, p<0.05), respectively. The quality of post-resection recording correlated with functional status of both the nerves determined 9 months after the surgery (R=0.51, p<0.001 for nerve III and R=0.57, p<0.01 for nerve VI). Even a trace or pathological response to the post-resection stimulation was associated with improved functional status (90% vs. 50%, p<0.05 for nerve III and 93% vs. 38%, p<0.01 for nerve VI)., Conclusions: Neurophysiological monitoring of ocular motor nerves enables their intraoperative identification during resections of the cavernous sinus meningiomas. Intraoperative monitoring of nerve III is particularly important in the case of tumors with extra- and intracavernous location, and the monitoring of nerve VI in the case of intracavernous tumors. The outcome of the post-resection monitoring has prognostic value with regard to the clinical status of the nerves on long-term follow-up., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background and Purpose: The pathogenesis of cerebral aneurysms still raises some controversies. The aim of this study was to identify morphological, hemodynamic, and clinical independent risk factors for anterior communicating artery (ACoA) aneurysm development., Methods: Computed tomography angiography and transcranial color-coded sonography were performed in 77 patients with a nonbleeding ACoA aneurysm and in 73 controls. Symmetry of A1 segments of the anterior cerebral arteries, angles between A1 and A2 segments, tortuosity, diameter, mean velocity (Vm), pulsatility index, and volume flow rate in both A1 segments were determined. Moreover, all study participants completed a survey on their medical history. Multivariate backward stepwise logistic regression analysis was performed to identify independent risk factors for ACoA aneurysm development., Results: Smoking, hypertension, asymmetry of A1 segments, the angle between A1 and A2 segments, A1 segment diameter, Vm, pulsatility index, and volume flow rate turned out to be associated with the occurrence of ACoA aneurysms on univariate analysis. Multivariate analysis identified smoking (odds ratio, 2.036; 95% confidence interval, 1.277-3.245), asymmetry of A1 segments>40% (odds ratio, 2.524; 95% confidence interval, 1.275-4.996), pulsatility index (odds ratio, 0.004; 95% confidence interval, 0.000-0.124), and the angle between A1 and A2 segments≤100° (odds ratio, 4.665; 95% confidence interval, 2.247-9.687) as independent strong risk factors for ACoA aneurysm development., Conclusions: The risk of ACoA aneurysm formation is determined by several independent clinical, morphological, and hemodynamic factors. The strongest independent risk factors include smoking, asymmetry of A1 segments>40%, low blood flow pulsatility, and the angle between A1 and A2 segments≤100°., (© 2014 American Heart Association, Inc.)

Objective: The etiology of hemodynamic disturbances following embolization or surgical resection of arteriovenous malformations (AVMs) has not been fully explained. The aim of the study was the assessment of the selected hemodynamic parameters in patients treated for cerebral AVMs using transcranial color-coded Doppler sonography (TCCS)., Materials and Methods: Forty-six adult patients (28 males, 18 females, aged 41 ± 13 years, mean ± SD) diagnosed with AVMs who were consecutively admitted to the Department of Neurosurgery between 2000 and 2012 treated surgically or with staged embolization were enrolled in the study. All patients were examined with TCCS assessing mean flow velocity (Vm), the pulsatility index (PI) and vasomotor reactivity (VMR) in all main intracranial arteries. The examined parameters were assessed in the vessel groups (feeding, ipsilateral and contralateral to the AVM) and they were compared between the examinations, i.e. at admission, within 24h after the first embolization or surgical resection (I control), and before the second embolization (II control)., Results: In feeders which were completely obliterated or surgically resected--I control examination showed a nonsignificant Vm decrease. The difference between Vm before embolization and II control examination was significant (102.0 ± 47.8 cm/s vs 54.3 ± 19.4 cm/s, p<0.01). A significant increase in PI (0.72 ± 0.18 vs 0.94 ± 0.24, p<0.01) and VMR (1.80 ± 0.59 vs 2.78 ± 0.78, p<0.01) of feeding vessels was observed in I control. No further increase in PI or in VMR was observed. In embolized feeding vessels after partial AVM embolization I control examination showed a significant decrease in Vm (116.1 ± 32.6 cm/s vs 93.4 ± 33.0 cm/s, p<0.01). No further significant decrease in Vm was noted. The pulsatility index increased significantly (I control, 0.54 ± 0.11 vs 0.66 ± 0.15, p<0.01) and then decreased nonsignificantly (II control). No statistically significant differences were found in VMR values between pretreatment, I and II control examinations. Both Vm in the ipsilateral internal carotid artery and the ratio of Vm of the embolized vessel to Vm of the corresponding contralateral vessel were significantly higher in I control examination compared to II control examination (111.8 ± 44.0 cm/s vs 101.3 ± 40.6 cm/s, p<0.01; 1.63 ± 0.61 vs 1.37 ± 0.62, p<0.01; respectively). No statistically significant correlation was observed between the decrease in Vm or the increase in PI in the embolized vessels and the reduction of AVM volume. In the nonembolized feeding vessels after partial AVM embolization II control examination revealed the increase in Vm and a significant decrease in PI (0.71 ± 0.21 vs 0.62 ± 0.16, p<0.01) compared to I examination. No statistically significant changes in the VMR value in the nonembolized feeders between the pretreatment, I and II control examinations were noted., Conclusions: The decrease in Vm and the increase in the PI in the embolized feeding vessels after the first complete embolization or surgical resection is observed, whereas the PI returned to normal values before Vm does. The observed decrease in Vm and an increase in the PI in embolized AVM feeders after complete or partial embolization do not correlate with the extent of embolization. In these vessels a relative increase in blood flow velocity is maintained within the first 24h following embolization as compared to contralateral vessels. The increase in Vm is not related to disturbances in VMR. Blood redistribution to the nonembolized AVM feeders is observed after partial AVM embolization., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Malignant transformation among gliomas WHO II ranges between 35% and 89%. However, according to some reports, all gliomas WHO II undergo such transformation over time. The aim of the study was to analyse MRI parameters indicating anaplastic transformation of gliomas WHO II., Material and Methods: Forty-six consecutive patients were enrolled in the study (20 females and 26 males; range of age 36 ± 9 years) with supratentorial glioma WHO II. Multiparametric MR examination included morphological imaging, perfusion-weighted imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy. Group division depended on the course of disease (ST - stable group, AT - anaplastic transformation group)., Results: Subtotal tumour resection was achieved in the whole AT group, whereas in the ST group, total tumour resection was achieved in 10/29 (34%) patients. The size of the residual tumour after surgery was statistically significantly higher in the AT group compared to the ST group (AT: 51.5 cm³ ± 37.7 vs. ST: 29.0 cm³ ± 37.9; p = 0.011). Contrast enhancement in the AT group occurred in 5/11 (45%) of tumours and in none of the patients' areas of contrast enhancement were resected during surgery/biopsy. However, the initial MR showed contrast enhancement in 10/29 (34%) of patients in the ST group. The areas of contrast enhancement were totally resected in all patients. Compared to the ST group tumours that underwent anaplastic transformation had statistically significantly higher values of mean nrCBV and max nrCBV on the initial MR, the follow-up and final MR examinations. However, statistically significant differences between the groups in ADC values were observed on the follow-up and final MR whereas mean Cho/Cr and mean Cho/NAA were observed as late as on the final MR examination., Conclusions: Multiparametric MR examination allows the detection of LGGs with high probability of rapid anaplastic transformation and the detection of transformation prior to the occurrence of contrast enhancement. The value of nrCBV is the most useful in the diagnosis of anaplastic transformation. The resection of contrast enhancement area of the tumour significantly increases time to anaplastic transformation of LGGs.

Background and Purpose: Reoperations of patients with recurrent low-grade gliomas (LGG) are not always recommended due to a higher risk of neurological deficits when compared to initial surgery. The purpose of the present study was to evaluate surgical outcomes of patients operated on for recurrent LGG., Material and Methods: Sixteen patients who had surgery for recurrent LGG out of 68 LGG patients who underwent surgery at the Department of Neurosurgery in Sosnowiec, Poland between 2005 and 2011 were enrolled in the study., Results: A large tumour volume prior to the initial surgery was the most significant parameter influencing LGG progression (96.6 cm³ vs. 47.9 cm3, p = 0.01). Increased incidence of epileptic seizures and decreased mental ability according to Karnofsky score were the most common symptoms associated with tumour recurrence. In the group of patients with malignant transformation, the relative cerebral blood volume (rCBV) was considerably increased (1.21 vs. 2.41, p < 0.01). No statistically significant difference was found in terms of the extent of resection between initial surgery and reoperation. Similarly, no significant difference was found in the number of patients with a permanent neurological deficit after initial surgery and reoperation., Conclusions: Reoperations of the patients with recurrent LGG are not burdened with a higher risk of neurological sequelae when compared to initial surgery. The extent of resection during the surgery for LGG recurrence is comparable to initial surgery. The increase of rCBV seems to be a significant biomarker that indicates malignant transformation.

Objective: A prospective volumetric analysis of extent of resection (EOR) was carried out to assess surgical outcomes in adults diagnosed with hemispheric low grade gliomas (LGGs)., Materials and Methods: 68 consecutive patients diagnosed with LGGs were enrolled in the study. Pre- and post-operative tumor volumes and EOR were measured based on FLAIR MRI. Dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) was used for the assessment of relative cerebral blood volume (rCBV). Three outcome measures were assessed: overall survival (OS), progression-free survival (PFS), and malignant degeneration-free survival (MFS)., Results: In 6 (9%) patients permanent neurologic deficits were observed. No statistically significant dependence between the EOR and the occurrence of permanent deficits was found. The eloquent or close to the eloquent location was statistically connected with lower EOR (p=0.023). The preoperative volume of tumors treated with gross total resection was significantly smaller than the volume of tumors in subtotal or partial resection groups (p=0.020, p<0.001, respectively). OS was predicted by age at diagnosis (p=0.032), and rCBV (p=0.002). Progression and malignant transformation occurred in 22 (32%) and 11 (16%) out of 68 patients. PFS was predicted by preoperative tumor volume (p=0.005), postoperative tumor volume (p=0.008), the EOR (p=0.001), and by the rCBV (p=0.033). MFS was predicted by preoperative tumor volume (p=0.034), the EOR (pp=0.020), and by rCBV (p=0.022). Postoperative tumor volume was associated with a trend of improved MFS (p=0.072). The univariate analysis shows the statistical trend for the relationship between histological subtype and PFS and MFS (p=0.079, p=0.078, respectively). Multivariate analysis selected preoperative tumor volume and rCBV as independently associated with PFS (p=0.009, p=0.019, respectively) and MFS (p=0.023, p=0.035, respectively). EOR was associated with a trend of improved PFS, and MFS (p=0.069, p=0.094, respectively)., Conclusions: Tumor resection of LGG with the use of intraoperative monitoring and neuronavigation is associated with a low risk of new permanent deficits, but EOR significantly decreases with the size of the tumor and/or its location in/close to the eloquent areas. Smaller preoperative tumor volume and greater EOR are significantly associated with longer OS, PFS and MFS. Preoperative rCBV is one of the important prognostic factors significantly connected with survival. Prognosis in LGGs is still under discussion. Other factors such as age, histopathological subtype and KPS should not be underestimated., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The aim of the study was to present consecutive stages of the partial transcondylar approach. Six simulations of the partial transcondylar approach were performed on non-fixed human cadavers without any known pathologies in the head and neck. The consecutive stages of the procedure were documented with photographs and diagrams. The starting point for the partial transcondylar approach is a posterior repositioning of the suboccipital segment of the vertebral artery. The approach is achieved by partial removal of the occipital condyle and lateral mass of the atlas as well as by suboccipital craniectomy. Elevation of the cerebellar hemisphere presents an important supplement of the approach. The partial transcondylar approach is a reproducible technique, which provides surgical penetration of the anterior part of the cranio-cervical junction and related regions. This approach is particularly useful in the treatment of intradural tumours localized ventrally to the medulla.

Background and Purpose: The partial transcondylar approach (PTA) is an alternative to the suboccipital approach in the surgical treatment of meningiomas of the anterior portion of the craniovertebral junction (APCVJ). The purpose of this study is to present our results of treatment of these meningiomas using PTA., Material and Methods: Fourteen patients (11 women, 3 men) with meningioma of the APCVJ were included in the study. Neurological status of the patients was assessed before and after surgery as well as at the conclusion of the treatment. The approximate volume of the operated tumour, its relation to large blood vessels, cranial nerves and brainstem, along with its consistency and vascularisation were assessed., Results: The symptom duration ranged from 1 to 36 months (median: 11 months). In 79% of patients, motor deficits of the extremities were predominant symptoms. Less frequent symptoms included headache, cervical pain and sensory deficits of cervical nerves C2 to C5. Approximate volume of the tumours ranged from 2.5 mL to 22.1 mL (mean: 11.7 mL). Gross total or subtotal resection was achieved in 86% of patients. The postoperative performance status improved in 57%, did not change in 36% and deteriorated in 7% of the patients., Conclusions: The PTA is a useful technique for removal of meningiomas expanding intradurally of the APCVJ without significant compression of the medulla. The results of treatment were good in most patients.

Background and Purpose: Mucocoele of the paranasal sinuses falls within the scope of interest for neurosurgery when erosion of the sinus wall and the osseous structures of the skull base develops and the lesion extends towards the cranial cavity, the orbit, the cavernous sinus or the sella turcica. The pa-per aims to present the method of treatment of extensive mucocoele which is used in our clinic., Material and Methods: We treated 7 patients (2 women and 5 men; age range: 27-68 years). Mucopyocoele was diagnosed in two cases, and mucocoele in the other five. In 5 cases, extension of the mucocoele to the cranial cavity and the orbit or to the ethmoid sinus and the orbit was observed. In the remaining 2 cases, mucopyocoele extended to the ethmoid sinus, the sphenoid and maxillary sinuses, cranial cavity and the orbit. The purpose of surgery was to remove the mucocoele or the mucopyocoele and to prevent recurrence., Results: The postoperative course in all 7 patients was uneventful. All symptoms gradually receded. No relapse was observed in any patient during a follow-up period that varied from 10 months to 8 years; nor did incidents of inflammation of collateral sinuses occur., Conclusions: The treatment of mucocoele or mucopyocoele of the frontal sinus penetrating to the cranial cavity and the orbit consists of the following stages: cranialization of the frontal sinus, complete resection of the mucosa, tight closing of the frontal-nasal duct, and separating the air space of the opened collateral nasal sinuses from the cranial cavity with a large pedicled periosteal flap.

Background and Purpose: The applied approach to the jugular foramen is a combination of the juxtacondylar approach with the subtemporal fossa approach type A. The purpose of this study is to present our results of treatment of jugular paragangliomas using the aforementioned approach., Material and Methods: Twenty-one patients (15 women, 6 men) with jugular paragangliomas were included in the study. The neurological status of the patients was assessed before and after surgery as well as at the conclusion of treatment. The approximate volume of the tumour, its relation to large blood vessels, cranial nerves and brainstem, as well as consistency and vascularity were also assessed., Results: The duration of symptoms ranged from 3 to 74 months. In 86% of patients hearing loss was the predominant symptom. The less frequent symptoms included pulsatile tinnitus in the head, dysphagia and dizziness. Approximate volume of the tumours ranged from 2 to 109 cm3. A gross total resection was achieved in 71.5% of patients. The postoperative performance status improved in 38% of patients, did not change in 38% and deteriorated in 24% of patients., Conclusions: A proper selection of the range of the approach to jugular foramen paragangliomas based on their topography and volume reduces perioperative injury without negative consequences for the radicality of the resection.

This study presents consecutive stages of the approach to the jugular foramen and related structures. Eleven simulations of the approach were performed on non-fixed human cadavers without any known pathologies in the head and neck. The consecutive stages of the procedure were documented with photographs and schematic diagrams. The starting point for the discussed approach is removal of the mastoid and petrosal parts of the temporal bone, as well as the jugular process and the jugular tuberculum. It allows penetration of the jugular foramen from the back. Widening of the approach enables penetration of the jugular foramen from above and the front. Approach to the jugular foramen is a reproducible technique, which provides surgical penetration of this foramen and related structures. This approach is particularly useful in the surgical treatment of tumours expanding in the petrous pyramid, surroundings of the petrosal part of the internal carotid artery, cerebellopontine angle, subtemporal fossa and nervous-vascular bundle of the neck.

Background and Purpose: The fronto-temporo-orbito-zygomatic approach (FTOZA) is an alternative to the pte-rional approach in surgical resection of meningiomas of the medial part of the lesser wing of the sphenoid bone. The purpose of this study is to present our results of treatment of these meningiomas using the FTOZA., Material and Methods: Thirty patients (19 women, 11 men) with a central skull base tumour were included in the study. The neurological status of the patients was assessed before and after surgery as well as at the conclusion of treatment. The approximate volume of the operated tumour, its relation to large blood vessels, cranial nerves and brainstem, as well as consistency and vascularisation were assessed., Results: The symptom duration ranged from 1 to 36 months (median: 6 months). Impaired visual acuity was the predominant symptom in 27.5% of patients. Less frequent symptoms included paresis/paralysis of the third cranial nerve, headache, psychoorganic syndrome and epilepsy. Approximate volume of the tumours ranged from 5 to 212 mL (median: 63 mL). Total or subtotal resection was achieved in 77% of patients. The postoperative performance status improved in 16.5%, did not change in 52.8% and deteriorated in 26.4% of patients. One (3.3%) patient died after the surgery., Conclusion: The FTOZA is a useful technique for removal of tumours expanding superiorly to the middle cranial fossa base without significant compression of the brain. Ability to remove tumours through the described approach decreases as the degree of infiltration of the clivus increases.

This paper presents consecutive stages of the fronto-temporo-orbito-zygomatic approach (FTOZA). Two simulations of FTOZA were performed on non-fixed human cadavers without any known pathologies in the head and neck. The consecutive stages of the procedure were documented with photographs and schematic diagrams. The starting point for FTOZA is a pterional craniotomy and osteotomy including the orbital rim, body of the zygomatic bone and zygomatic arch. In justified cases it is also possible to temporarily remove the upper and lateral walls of the orbit. Wide drawing apart of the Sylvian fissure is an important supplement of the approach. The fronto-temporo-orbito-zygomatic approach is a reproducible technique, which provides surgical penetration of the middle cranial fossa and related regions. This approach is particularly useful in the treatment of tumours of the above-mentioned anatomical areas as well as vascular malformation of the posterior part of the arterial circle of the brain.

Background and Purpose: The aim of the study was to present our results of the surgical treatment of subtemporal fossa tumours and surrounding regions using the extended subtemporal approach., Material and Methods: Twenty-five patients (10 women, 15 men) with subtemporal fossa tumours were included in the study. The neurological and performance status of the patients were assessed before and after surgery as well as at the conclu-sion of treatment. The approximate volume of the operated tumour, its relation to large blood vessels and cranial nerves, as well as consistency and vascularisation were assessed., Results: The symptom duration ranged from 2 to 80 months (mean: 14 months). In 44% of patients, headache was the predominant symptom. Less frequent symptoms were: paralysis of the abducent nerve and disturbances of the trigeminal nerve. Approximate volume of the tumours ranged from 13 to 169 cm3 (mean: 66 cm3). The most frequent histological diagnosis was meningioma (16%), followed by angiofibroma, neurinoma and adenocystic carcinoma (12%). Total or subtotal resection was achieved in 80% of patients., Conclusions: The extended subtemporal approach allows for the removal of tumours of the subtemporal fossa and surrounding regions. This approach also allows one to remove tumours expanding in the regions surrounding the subtemporal fossa only. In such cases the subtemporal fossa constitutes the way of the surgical approach.

The aim of the study was to present consecutive stages of the extended subtemporal approach (ESA). Seven simulations of ESA were performed on non-fixed human cadavers without any known pathologies in the head and neck. The consecutive stages of the procedure were documented with photographs and schemes. The starting point for ESA is osteotomy of the zygomatic arch and craniectomy including the greater wing of the sphenoid bone. Dislocation or removal of subtemporal fossa contents allows one to penetrate its inside and related structures. Additional widening of inspection allows osteotomy of the condyloid process of the mandible. ESA is a reproducible technique which provides surgical penetration of the subtemporal fossa and related structures. This approach is particularly useful in the surgical treatment of tumours expanding in the orbit, maxillary sinus, pterygopalatine fossa, nasopharynx, sphenoid sinus, cavernous sinus, parapharyngeal space, retromandibular fossa and surroundings of the petrosal part of the internal carotid artery.

Background and Purpose: To present our results of the surgical treatment of central skull base tumours using the extended subfrontal approach (ESA)., Material and Methods: Twenty-six patients (8 women, 18 men) with central skull base tumours were included in the study. The neurological and performance status of the patients was assessed before and after surgery as well as at the conclusion of treatment. The approximate volume of the operated tumour, its relation to the large blood vessels, cranial nerves and brainstem, as well as consistency and vascularisation were assessed., Results: The symptom duration ranged from 1.5 to 18 months (mean: 8.3 months). Loss of olfaction was the predominant symptom in 38% of patients. Less frequent symptoms were: paresis/paralysis of the 6th cranial nerve, psychoorganic syndrome, impaired visual acuity, nasal obstruction and headache. Approximate volume of the tumours ranged from 10 to 105 ml (mean: 54.3). The most frequent histological diagnosis was chordoma (19%), meningioma (15%), followed by haemangiopericytoma, fibroma and esthesioneuroblastoma (12%). Total or subtotal resection was achieved in 77% of patients. The postoperative performance status was improved in 39%, unchanged in 27% and impaired in 15% of patients. Five patients died after the surgery., Conclusions: Extended subfrontal approach is a useful technique for removal of benign tumours expanding along the midline, superiorly and inferiorly to the skull base. For removal of malignant tumours at the same location, ESA is an alternative to a combination of transcranial approach and one of the craniofacial approaches.

Objective: It is presumed that increased blood flow through the single azygos anterior cerebral artery (Az) may contribute to the formation of an Az aneurysm. The aim of this study was to assess the blood flow velocities in the arteries of the anterior cerebral artery (ACA) complex in patients with the Az aneurysm., Patients and Methods: A series of three patients (2 men, aged: 65, 52 and 41) with an aneurysm (unruptured in two cases) of the distal Az was examined. Blood flow velocities in the Az and the A1 segment of the ACA were measured by means of a transcranial color-coded duplex sonography (TCCS) and the Az to A1 segment (Az/A1) velocity ratio was calculated. The control group consisted of 22 healthy subjects (mean age: 44 years)., Results: There was a trend toward decreased (p=0.06) mean blood flow velocity in the Az compared to the A2 segment of the ACA of the control group. Blood velocity in the A1 segment did not differ between the study and control groups. Pulsatility and resistance indices in the Az were similar to those in the A2 segment of the control group. There were no differences between the Az/A1 ratio in the study group and the A2/A1 velocity ratio in the control group., Conclusion: Our results suggest that Az aneurysms are not associated with increased blood flow velocity in the Az. Possibly, a hemodynamic stress related to the Az bifurcation geometry, together with a bent course of this artery around the genu of the corpus callosum, predispose to aneurysm formation.

Background and Purpose: The aim of this study was to present results obtained by the authors after surgical treatment of tumours involving the cavernous sinus (CS) and its surroundings., Material and Methods: Thirty-eight patients (23 females and 15 males) with tumours of the CS and its surroundings were included in the study. The neurological condition of patients and their ability to perform activities of daily living were evaluated prior to treatment, postoperatively and after completion of therapy. The following parameters were measured: approximate volume of the operated lesions; their relation to larger vessels, cranial nerves and the brainstem; consistency and vascularization., Results: The medical history of the disease ranged from 1.5 to 48 months, mean 12 months. In 89.5% of cases impaired ocular motility on the side of the lesion was the symptom indicative of the condition. The second most common group of symptoms (29%) included impairments of trigeminal nerve function. The approximate volume of all resected tumours ranged from 0.6 to 60 mL (mean 12.2 mL). In 50% of cases the resected tumours were diagnosed as meningiomas. The remaining entities included: perithelioma, hypophyseal adenoma, adenoid cystic carcinoma, neuroendocrine carcinoma, trigeminal neurinoma, chordoma, cavernous angioma and lymphoma. In 63% resections were complete. Functional capacity of patients improved in 34% of cases, remained unchanged in 53%, deteriorated in 10.5%, and one patient died., Conclusions: Surgical intervention involving the CS and its surroundings enables resection of neoplastic tumours of this anatomical region with satisfactory clinical results and low mortality. Most patients suffer from temporary paresis or paralysis of the oculomotor, trochlear and abducent nerves. Reduction of completeness of resections of CS tumours decreases the number of postoperative neurological deficits without a significant increase in the rate of lesion regrowth.

We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.

Cerebral aneurysms coexistent with iatrogenic (after surgical ligation or occlusion) or idiopathic (due to atheromatosis) occlusion of an extracranial cerebral artery are very rare. The occlusion of the brachiocephalic vessels leads to the formation of a collateral circulation at two levels: the circle of Willis and the connections between collaterals of the extracranial cerebral arteries. The authors discuss different types of collateral arterial pathways as well as hemodynamic abnormalities in the case of the occlusion of the brachiocephalic vessels, particularly internal carotid artery or the innominate artery occlusion. The paper analyses the etiopathogenesis of cerebral aneurysms in view of the hemodynamic theory of cerebral aneurysms formation. The article is illustrated with own three cases of ruptured cerebral aneurysms coexistent with the occlusion of the innominate artery.

A 61-year-old man with severe factor XII deficiency presented with a subdural hematoma appearing as mixed but mainly high density by computed tomography in the left frontotemporoparietal region. No cranial injury was reported in the medical history of the patient. Clotting system study showed less than 1% functional activity of factor XII, whereas the levels of the other clotting factors were within the normal ranges. Partially clotted and hemolyzed subdural hematoma was removed through a craniotomy. The postoperative course was uneventful. The patient later died of severe circulatory-respiratory failure. We believe that the subdural hematoma may have developed as a result of a minor head trauma sustained in the past. We suggest that impairment of fibrinolytic activation related to severe factor XII deficiency might have contributed to the delay of dissolution of the subdural hematoma which, under ordinary circumstances, would have formed chronic subdural hematoma.

Objective: The objective of this study was to assess the collateral circulation and blood flow velocity in arteries forming collateral circulation in patients with cerebral aneurysms and the occlusion of the brachiocephalic vessels., Methods: Between 1989 and 2004 we examined a group of seven consecutive patients with diagnosed cerebral aneurysm and occlusion of the extracranial artery by means of cerebral angiography, transcranial color-coded sonography (TCCS) and color Doppler sonography of extracranial arteries. The Doppler examination results achieved in this group were compared with the Doppler results of 40 healthy subjects from a control group., Results: Three patients were diagnosed with an occluded innominate artery. In four other cases an occlusion of the extracranial segment of the internal carotid artery was found. The aneurysms were located on intracranial arteries of collateral flow. The innominate artery occlusion resulted in a hemodynamic effect which was a complete vertebral steal and systolic deceleration (in one case) or alternating flow (in two cases) in the right common carotid artery. An additional route of collateral circulation in all these cases led from extracranial carotid branches through the right external carotid artery to the ipsilateral internal carotid artery. In all seven patients, 13 intracranial collateral pathways were examined. In eight of them, including four cases with cerebral aneurysms, an increase in blood flow velocity was observed. In the remaining five cases, including three cases with cerebral aneurysms, the mean blood velocity was within the normal range. The anterior communicating artery (AComA) formed the main intracranial collateral pathway which was found in seven patients, including three patients with diagnosed AComA aneurysm. Blood flow velocity in ipsilateral (on the obstructed side) and contralateral (on the unobstructed side) anterior cerebral artery, as well as pulsatility and resistance indexes in contralateral anterior cerebral and middle cerebral arteries were higher compared with healthy control subjects. In the ipsilateral middle cerebral artery a relative, insignificant decrease of pulsatility and resistance indexes was detected. Ipsilateral and contralateral middle cerebral artery blood flow velocities were lower compared with the control group., Conclusion: Occlusion of the brachiocephalic vessels leads to formation of collateral circulation through the circle of Willis and the extracranial collaterals connecting the external and internal carotid arteries. An increase in blood flow velocity is commonly observed in intracranial arteries forming a collateral pathways. In some cases, not excluding arteries with a cerebral aneurysm, the increase in blood flow velocity is insignificant or none at all. This study shows that formation of a cerebral aneurysm is not always related to an increase in the flow velocity of collateral arteries.

The authors present a case of a 47-year-old female in whom there was diagnosed a chronic calcified subdural empyema 46 years after the removal of an acute subdural empyema resulting from complications after otitis media. The patient had suffered from grand mal convulsions and partial epileptic seizures occurring 3-4 times a month. A large frontotemporoparietal craniotomy was carried out and the subdural empyema filled with numerous brownish-black, uncharacteristic tissue fragments together with the partially calcified and ossified capsule was removed. The empyema mass was found to be sterile for bacteria. After the operation, mental disability symptoms began to withdraw and the number of epileptic seizures decreased.

The present study was carried out in 12 patients (7 males and 5 females) aged 16-56 years (mean age 35.9) with arteriovenous malformation diagnosed in cerebral angiography. The examination was performed by means of ATL ULTRAMARK 9 with low-frequency (2MHz to 3MHz) transducer. Assessment was made of possibilities of imaging arteriovenous malformations by transcranial colour-coded duplex sonography and of blood flow values in the studied intracranial arteries. Statistical analysis was applied of the following blood flow parameters: mean velocity, peak systolic velocity, end diastolic velocity, pulsatility index (PI), resistance index (RI), pulsatility transmission index (PTI) and relative flow velocity (RFV). The malformations were imaged using TCCS in 9 (75%) patients. In two-dimensional B mode image the angiomas displayed echogenicity similar to the surrounding brain parenchyma and could not be precisely delineated. The colour-coded imaging made possible depicting the image of the vessel loops in the AVM nidus. In two other patients the presence of angiomas was confirmed by blood flow disturbances in the feeder vessel: increased blood flow, decreased pulsatility and resistance indices, and collateral circulation. Collateralization by the contralateral internal carotid artery via the anterior communicating artery was disclosed in 9 cases. The TCCS results corresponded closely to angiographic findings. Collateral circulation via the posterior communicating artery ipsilateral to the AVM was found in 3 of 5 patients in whom it was diagnosed in cerebral angiography. Doppler findings in the patients were similar to the conventional TCD examination. In the feeding vessels significant increase in blood flow velocity and decreased pulsatility and resistance indices was observed. RFV value for the end diastolic velocity was higher than RFV for the peak systolic velocity (p < 0.001) and mean velocity. These findings suggest that the increased end diastolic velocity in the feeding vessel is higher than the mean velocity and peak systolic velocity. It is thought that the TCCS can be successfully used in early diagnosis of cerebral arterio-venous malformations and as an instrument in follow-up examination.