BDNF, sHLA-G, and sTREM-1 are useful blood biomarkers for identifying grade IV glioma patients.

Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble triggering receptor expressed on myelocytes) and increased levels of IL-10 in all grades of glioma patients in comparison with healthy controls (sTREM-1: grade II: p=0.0051, grade III: p=0.02, grade IV: p=0.01; IL-10: grade II: p=0.0017, grade III: p=0.03, grade IV: p=0.007). However, we did not find any combination of tested markers with good sensitivity and specificity in grades II and III of glioma patients to discriminate them from healthy controls. In grade IV glioma patients, two sets of markers showed promising results in distinguishing patients from healthy people. For the first set consisting of four selected markers, sTREM-1, sHLA-G, BDNF, and IL-13, the ROC curves indicate a good discriminatory capability for glioblastoma patients (AUC=0.9510). The best discriminatory capability for glioblastoma patients (AUC=0.9534) was found for the second set consisting of three selected markers sTREM-1, sHLA-G, and BDNF with 79.2% sensitivity and 94.1% specificity.

HLA-G 5'URR regulatory polymorphisms are associated with the risk of developing gliomas.

BACKGROUND: Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 HLA-G 5'URR variants, sHLA-G level and clinical variables in glioma patients. METHODS: We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The HLA-G 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA. RESULTS: Haploblock within HLA-G 5'URR consisting of -762T, -716G, -689G, -666T, -633A, followed by -486C and -201A alleles were significantly more frequent in patients with gliomas than in the controls (p < 0.05). No correlation of HLA-G 5'URR variants with sHLA-G plasma level was found. Analysis of HLA-G 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, -666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers (p = 0.04). CONCLUSION: Our results suggest genetic association of HLA-G 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.

Navigated 3D-ultrasound power Doppler and visualization of lenticulostriate arteries during resections of insular gliomas.

•Preservation of LSAs is extremely important during resections of insular gliomas.•Navigated 3D-US power Doppler may enable intraoperative visualization of LSAs.•Quality of ultrasound scanner is important when LSAs should be visualized.•Reliability of LSAs depiction by 3D-US power Doppler is still investigated.

HLA-G 14bp Ins/Del Polymorphism, Plasma Level of Soluble HLA-G, and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients also had higher plasma levels of sHLA-G. Patients with methylated MGMT promoters had lower levels of sHLA-G than those with unmethylated MGMT promoters. The level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut-off value of 40 U/mL survived significantly longer than patients with sHLA-G levels above 40 U/mL. The levels of sHLA-G were also negatively correlated with the level of IL-6 (p = 0.0004) and positively with IL-10/IL-6 (p = 0.046). Conclusion: The presence of the 14 nt insert in both homozygous and heterozygous states of the HLA-G 14bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

Large Residual Pilocytic Astrocytoma After Failed Ultrasound-Guided Resection: Intraoperative Ultrasound Limitations Require Special Attention.

While benefits of neurosurgical intraoperative ultrasound (IOUS) are reported frequently, this method still has some significant pitfalls, which are described less often. However, sufficient knowledge on dealing with IOUS drawbacks, particularly various image artifacts, is important for successful surgery. We report a case of failed IOUS-guided pediatric cerebellar pilocytic astrocytoma resection, incorrectly evaluated as gross total resection according to IOUS. A large tumor residuum was left in place. Successful IOUS-guided reoperation using new IOUS technology and appropriate ultrasound imaging technique are described. The most probable reasons for initial resection failure and crucial points of reoperation, predominantly dealing with IOUS artifacts, are discussed. Neurosurgeons should be aware of IOUS limitations and have sufficient knowledge about how to overcome them before adopting routine use of this intraoperative imaging modality.

Extradural Characteristics of the Origins of Lumbosacral Nerve Roots.

BACKGROUND AND STUDY AIMS: A great number of unsuccessful intervertebral herniated disk surgeries in the lumbosacral region have highlighted the importance of a comprehensive knowledge of the different types of nerve root anomalies. That knowledge gained by anatomical studies (and intraoperative findings) might contribute to better results. In our study we focused on intraspinal extradural lumbosacral nerve root anomalies and their possible role in radiculopathy. MATERIAL AND METHODS: The study was performed on 43 cadavers within 24 hours after death (32 men and 11 women). Bodies were dissected in the prone position, and a laminectomy exposed the entire spinal canal for the bilateral examination of each spinal nerve root from its origin to its exit through the intervertebral foramen or sacral hiatus. Uncommon extradural features in the lumbosacral region were pursued and documented. The spinal dural sac was also opened, aimed at recognizing the normotyped, prefixed, or postfixed type of plexus. RESULTS: A total of 20.93% of anomalies of extradural lumbosacral nerve root origins were observed, with the normotyped plexus prevailing. We observed atypical spacing of exits of lumbosacral roots (four cases), two roots leaving one intervertebral foramen (one case), extradural anastomoses (two cases), and missing extradural nerve root courses (two cases). The results were differentiated according to the normotyped, prefixed, or postfixed plexus type. CONCLUSION: Results of similar studies dealing with anomalies of lumbosacral nerve roots were aimed at improving the results of herniated disk surgeries because ∼ 10% of misdiagnoses are related to ignorance of anatomical variability. Our observations may help explain the differences between the clinical picture and generally accepted anatomical standards.

Navigated 3D-ultrasound versus conventional neuronavigation during awake resections of eloquent low-grade gliomas: a comparative study at a single institution.

BACKGROUND: The data showing usefulness of navigated 3D-ultrasound (3DUS) during awake resections of eloquent gliomas are sparse. Results of surgeries performed using 3DUS were never compared to procedures guided by standard neuronavigation. The aim of this work is to assess the effectiveness of 3DUS during awake resections of eloquent low-grade gliomas (LGGs) by comparing surgical results of two series of patients operated on using conventional neuronavigation and using 3DUS. To our knowledge, a similar study is lacking in the literature. METHODS: During a 4-year period (September 2006 to August 2010) 21 awake resections of LGGs guided by neuronavigation (series 1, S1) were consecutively performed in Department of Neurosurgery in Bratislava. During another 4-year period (August 2010 to July 2014) 28 awake resections of LGGs guided by 3DUS (series 2, S2) were consecutively conducted. In both patients series, the eloquent cortical and subcortical structures were intraoperatively detected by direct electrical stimulation. Extent of tumor resection (EOR) and functional outcome in both series were compared. RESULTS: EOR was significantly greater (p = 0.022) in S2 (median = 93.25%; mean = 86.79%), as compared to S1 (median 87.1%; mean = 75.85%). One permanent minor deficit in S1 and 2 minor deficits in S2 occurred, the difference was not significant (p = 0.999). CONCLUSIONS: Our work represents the first study comparing results of surgeries guided by 3DUS versus conventional navigation. The extent of awake resections of eloquent LGG guided by 3DUS was greater comparing to awake resections guided by standard neuronavigation; use of 3DUS had no impact on the number of new permanent deficits.

Intraspinal intradural variations of nerve roots.

PURPOSE: The aim of this work is to point out the intraspinal anatomical variations of nerve roots and their possible participation in radiculopathy. METHODS: The anatomical study was performed in 33 cadavers. There were 25 male cadavers aged 30-75 years and 8 female cadavers aged 45-77 years, with a mean age of 46.5 years to 24 h from death. All intradural rami communicantes between nerve roots were excised and examined histologically for the presence or absence of nervous tissue. The type of the plexus was defined by subtracting from the root C2. RESULTS: Findings of the normotype of plexus formation occurred in 24 cases (72.7%). Variations in its formation were observed in nine cases (27.3%). The prefixed type was observed in six cases (18.2%), postfixed type in three cases (9.1%). The formation of isolated prefixed or postfixed type of the brachial and lumbosacral plexus was not observed. Anatomical preparations revealed intradural variations in all cases of the lumbosacral plexus, 22 times (66.7%) in cases of cervical roots, and in the thoracic region seven times (21.2%). Variations occurred more frequently in variations of plexus formation. CONCLUSIONS: This study allowed us to identify and describe unpublished intraspinal intradural anatomical variations of nerve roots, and their interrelationships throughout the spinal canal with their potential influence on the clinical picture. Anatomical preparations revealed a higher incidence of intraspinal intradural variations, particularly between sacral roots. Reliance of their incidence of the plexus type was observed.

Intraspinal extradural variations of nerve roots.

INTRODUCTION: The aim of this work is to point out the intraspinal extradural anatomical variations of nerve roots and their possible participation in radiculopathy. METHODS: The anatomical study was performed in 33 cadavers at a mean age of 46.5 and up to 24h from death. All extradural anastomoses between nerve roots were excised and examined histologically for the presence or absence of nervous tissue. The type of the plexus was defined by subtracting from the root C2. RESULTS: Findings with the normotype of plexus formation prevailed in 24 cases (72.7%). Variations in its formation were observed in 9 cases (27.3%). The prefixed type in 6 cases (18.2%), post-fixed type in 3 cases (9.1%). We did not observe the formation of the isolated prefixed or post-fixed types in the brachial or lumbosacral plexuses. Extradural anatomical variations occurred in 20 cases (60.6%). They were more frequent on the left, in 10 cases (30.3%), bilateral in 3 cases (9.1%). In 8 instances (24.2%), the atypical spacing, including four in the lumbosacral region, was observed. Variations occurred more frequently in variations of formation of the plexus. CONCLUSIONS: This study allowed us to identify and describe unpublished intraspinal extradural anatomical variations of nerve roots and their interrelationships throughout the spinal canal with their potential influence on the clinical picture. Anatomical preparations revealed a higher incidence of intraspinal extradural variations, mainly between sacral roots. The reliance of their incidence of the type of plexus was observed.

Visualization of lenticulostriate arteries during insular low-grade glioma surgeries by navigated 3D ultrasound power Doppler: technical note.

OBJECTIVE Resection of insular gliomas is challenging. In cases of intraoperative injury to the lenticulostriate arteries (LSAs), the usual result is a dense hemiplegia. LSAs are usually localized just behind the medial tumor border but they can also be encased by the tumor. Thus, exact localization of these perforators is important. However, intraoperative localization of LSAs using conventional neuronavigation can be difficult due to brain shift. In this paper, the authors present a novel method of intraoperative LSA visualization by navigated 3D ultrasound (3DUS) power Doppler. This technique enables almost real-time imaging of LSAs and evaluation of their shift during insular tumor resections. METHODS Six patients harboring insular Grade II gliomas were consecutively operated on at the Department of Neurosurgery in Bratislava using visualization of LSAs by navigated 3DUS power Doppler. In all cases, the 3DUS data were repeatedly updated to compensate for the brain shift and display the actual position of LSAs and residual tumor. RESULTS Successful visualization of LSAs was achieved in all cases. During all surgeries, the distance between the bottom of the resection cavity and LSAs could be accurately evaluated; in all tumors the resection approached the LSAs and only a minimal amount of tissue covering these perforators was intentionally left in place to avoid injury to them. CONCLUSIONS Visualization of LSAs by navigated 3DUS power Doppler is a useful tool that may help to prevent injury of LSAs during removal of insular low-grade gliomas. However, reliability of this method has to be carefully evaluated in further studies.

Direct electrical stimulation of the optic radiation in patients with covered eyes.

Direct electrical stimulation (DES) of the optic radiation (OR) during an awake tumor resection has been repeatedly reported. In all cases, visual function monitoring was performed in patients with open eyes which were looking at a picture. We report a new modification of the standard method, OR stimulation in patient with closed and covered eyes. To the best of our knowledge, this method was not presented before. According to our first experience, this methodology may be in some cases a potentially more sensitive form of neuromonitoring than the OR stimulation in patients with open eyes, as the phosphenes elicited by DES may be more distinct in patients with covered eyes. The technique is discussed, and a literature review on intraoperative identification of the OR is presented as well. However, a future prospective study is needed to confirm the relevance of our finding.

Nonfunctioning pituitary adenomas: association of Ki-67 and HMGA-1 labeling indices with residual tumor growth.

BACKGROUND: The postoperative biological behavior of nonfunctioning pituitary adenomas (NFPAs) is variable. Some residual NFPAs are stable long-term, others grow, and some recur despite complete removal. The usual histological markers of tumor aggressiveness are often similar between recurring, regrowing, and stable tumors, and therefore are not reliable as prognostic parameters. In this study, the clinical utility of proliferation indices (labeling index, Li) based on immunohistochemistry targeted at antigens Ki-67 and High-mobility group A1 (HMGA-1) for prediction of NFPA prognosis was investigated. METHODS: Fifty patients with NFPAs were investigated. In each patient, Ki-67 and HMGA-1 Li were evaluated. Based on postoperative magnetic resonance images, patients were classified as tumor-free (18 patients), or harboring a residual tumor (32 patients). The latter group was further subdivided into groups with stable tumor remnants (11 patients) or progressive tumor remnants (21 patients). RESULTS: The median follow-up period was 8 years. No significant relationship between HMGA-1 Li and residual tumor growth was found. Growing residual tumors showed a trend towards higher Ki-67 Li compared with stable ones (p = 0.104). All tumor remnants with Ki-67 Li above 2.2% were growing. The relationship between residual tumor growth and Ki-67 Li exceeding the cutoff value of 2.2% was significant (p = 0.01 in univariate, p = 0.044 in multivariate analysis). CONCLUSIONS: The prognostic significance of the HMGA-1 antigen was not confirmed. In contrast, the Ki-67 Li provides useful and valuable information for the postoperative management of NFPAs. In residual adenomas with a Ki-67 Li above 2.2%, regrowth should be expected, and these tumors may require shorter intervals of follow-up magnetic resonance imaging (MRI) and/or early adjuvant therapy. Future larger studies are needed to confirm the results of this study.

Recurrent craniopharyngiomas in children and adults: long-term recurrence rate and management.

BACKGROUND: The significance of the majority of the factors influencing the recurrence rate (RR) of craniopharyngiomas remains unclear, and the management of this significance is controversial. The present study aimed to evaluate the influence of patient age and tumor topography on the RR, the efficacy of radiotherapy, and the safety of surgery for recurrences. METHODS: The RR was analyzed in 38 children (follow-up, 2-256 months [mean, 147.6]) and 63 adults (follow-up, 2-221 months [mean, 100.2]. The efficacy of 18 sessions of radiotherapy (13 patients) and the outcome of 52 secondary surgeries (37 patients) were evaluated. RESULTS: The RR reached 39.5% in children and 22.2% in adults (p = 0.053). After radical tumor removal, the RR in children (36.7%) was significantly higher (p = 0.024) than that in adults (14%). In children after radical removal of intraventricular and extraventricular craniopharyngiomas (IECs), the RR was higher (60%; p = 0.071) than in extraventricular (intrasellar and suprasellar; purely suprasellar extraventricular) tumors (25%). Radical removal of 50% of tumors was achieved (73.1% in children; 26.9% in adults; p = 0.002) in 56.7% of the first and 40.9% of further recurrences. There was no early mortality after 52 surgeries; functional worsening (endocrine, 2; obesity, 2; visual, 3) occurred after 7/52 secondary surgeries. Recurrence occurred after 9/18 sessions of radiotherapy. CONCLUSIONS: The RR was higher in children than in adults and in IECs relative to other topographic groups. Children with IECs represent a risk group. The efficacy of radiotherapy was inconclusive. Early detection of recurrences enabled safe excision with low morbidity.

Navigated three-dimensional intraoperative ultrasound-guided awake resection of low-grade glioma partially infiltrating optic radiation.

We report a case of awake resection of temporal low-grade glioma infiltrating the optic radiation (OR). The OR was localized by direct electrical stimulation (DES) and the tumor was delineated by navigated intraoperative 3D ultrasound. Ultrasound artifacts were eliminated by 3D-ultrasound data acquisition with a miniature probe inserted into the resection cavity. A total of 97 % resection was achieved, and small tumor portion involving OR was intentionally left in place. Functional result was partial quadrantanopia instead of more profound visual deficit, which would follow gross-total resection. To our knowledge, DES of OR was reported once; the aforementioned method of ultrasound artifact elimination has not been reported before.

Subtemporal transtentorial resection of cavernous malformations involving the pyramidal tract in the upper pons and mesencephalon.

BACKGROUND: Lateral approaches to the brain stem for the resection of the cavernous malformations are preferred in order to avoid the structures within the floor of the fourth ventricle. The entry behind the pyramidal tract (PT) is usually carried out through the posterolateral surface of the brain stem. The more straightforward lateral approach below the temporal lobe is used rarely because of potential risks. METHODS: The outcome after resection of the cavernomas involving the PT in the mesencephalon and the upper pons via the subtemporal transtentorial approach in nine patients was analysed. Mapping of the PT by direct electrical stimulation was used in the last four patients. RESULTS: The subtemporal transtentorial approach enabled adequate exposure of the lateral and anterolateral surface of the midbrain and the upper pons. No adverse events from the elevation of the temporal lobe were encountered. Direct electrical stimulation using a bipolar electrode with the parameters of 100 Hz, 1 ms, and 3-9 mA evoked motor responses in three of four patients. It allowed placing the incision in the lateral surface of the midbrain behind the PT or between the fibres of the upper and the lower extremity. No worsening of the PT functions was observed in the series. CONCLUSIONS: The subtemporal transtentorial approach enables adequate exposure of the lateral and the anterolateral surface of the mesencephalon and upper pons, allowing neurophysiological mapping of the PT and thus avoiding its damage during removal of the cavernoma.

Craniopharyngiomas in children: how radical should the surgeon be?

PURPOSE: Two main modes of management of craniopharyngiomas, namely, radical tumor removal and intentional incomplete removal followed by radiotherapy, are used. Recently, a half-way solution was added. Radical removal is reserved only for the tumors not involving hypothalamus. Such tumors, however, are not clearly defined. The goal of the study was to clarify the relationship of craniopharyngiomas with surrounding structures, especially hypothalamus, and to evaluate its clinical significance. METHODS: Our policy of management of craniopharyngiomas was elaborated on the basis of the results of morphological studies of the topography and their correlation with magnetic resonance imaging (MRI) in 115 adults and children operated on since 1991. Suitability of the policy in children and adolescents was verified by long-term outcome analysis in 41 consecutive patients. RESULTS: The rate of morbidity and mortality was higher in patients with craniopharyngiomas located inside the third ventricle either partially (intraventricular and extraventricular craniopharyngiomas, IEVCs, 16 patients) or completely (intraventricular, one patient) than in tumors located outside the ventricle (suprasellar extraventricular, SEVCs, five patients; intrasellar and suprasellar, 19 patients). Postsurgical hypothalamic signs and symptoms occurred most often in intraventricular tumors; there were no mental disorders or obesity caused by primary removal of SEVCs including those severely compressing hypothalamus. CONCLUSIONS: Radical removal of SEVCs is safer than of IEVCs despite an apparent involvement of hypothalamus. In majority of cases, they may be distinguished by indirect MRI signs; in others only according to operation findings; final decision about the optimal extent of tumor removal should be made during surgery.