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.

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.

Morphological Peculiarities of the Pelvic Autonomic Nervous System and Their Impact on Clinical Interventions in the Lesser Pelvic Region.

Background: The aim of the work is to define the morphological peculiarities of the pelvic autonomic nervous system (ANS) and their importance in the clinical and surgical interventions in the lesser pelvis. Material and methods: Anatomical variations in the formation of the pelvic ANS were observed in 20 cadavers. The study included 17 men (85%), aged 18 to 84, and 3 women, aged 27 to 86. The average age was 53.8 years. The subjects most often died by violent death in car accidents, by asphyxia, or by sudden death. The study was approved by the Ethics Committee of the Health Care Surveillance Authority, Bratislava, Slovakia. We studied cadavers without congenital or detected anomalies, cancer, deformities of the body, or spinal or abdominal surgeries within 24 h of death. We observed a relationship between the dimensions and the number of ganglia, as well as the number and course of nerve branches and anastomoses. In the pelvic area, we observed the hypogastric plexus superior, hypogastric plexus inferior, and the truncus sympathicus. In all cadavers, we clarified the lumbosacral plexuses after evisceration. In the lumbosacral region, the roots were defined based on their participation in the formation of the plexuses. To show the intimate relationship between both systems, we also focused on the details of the structure (rami communicantes) related to the connections of the ANS with the spinal nervous system. Results: Anatomical variations in the formation of the pelvic ANS were observed in all cases. We included cases with more than two truncus sympathicus ganglia as the segmental type. The segmental form occurred in 14 (70%) cases, and was concentrated in 6 (30%) cases. Rami communicantes provided anastomoses to the spinal nerves. Small ganglia were observed on the rami communicantes. With the concentrated type, we observed the division of the sympathetic and parasympathetic systems. With the segmental and concentrated forms, symptoms of the "diffuse form" may occur, which we observed in all cases. We observed significant right-left asymmetry and differences in the formation of ganglia and anastomoses. Conclusions: This study allowed us to identify and describe the morphological peculiarities of the pelvic ANS and their possible influence on the clinical picture. Asymmetry and dependence of their occurrence on the type of ANS was observed. The variations were frequent. Their preoperative diagnosis is difficult to impossible. The absence or lack of intraoperative vigilance can lead to the damage of pelvic ANS during operations and blockades of the pelvic plexus. The acquired knowledge can be helpful in clarifying clinical signs and symptoms of these conditions.

Extradural and intradural characteristics of the cervical nerve root anomalies.

The anomalous anatomical arrangement of the cervical spinal nerve roots within the spinal canal can complicate the surgical treatment of several pathologies. This work aimed to reveal intraspinal anatomical anomalies of the extradural and also intradural cervical spinal nerve roots courses. The anatomical study was realised in 43 cadavers with a mean age of 53.7 (32 men and 11 women). After opening the spinal canal and also the dural sac the intradural and extradural anomalies of the cervical spinal nerve roots (bilaterally) were explored and documented. We found completely 49 cases (56.98%) of intraspinal cervical nerve root anomalies. Extradural anomalies were found in 11 cases (12.79%) including atypical spacing, two roots exiting through one neuroforamen, extradural communications, aberrant root. Intradural anomalies observed in 28 cases (32.56%) comprised: communications between the dorsal roots and ventral roots separately or together and the multiple communications. Other anomalies (10 cases, 11.63%) included various types of atypical spacing of the roots and their asymmetry. All the results are differentiated according to the plexus type (pre-, postfixed, normotyped). This study describes intraspinal (extradural and intradural) anatomical anomalies of the cervical spinal nerve root courses. Knowledge of these variabilities should help to prevent the failure of several medical procedures.

Intraspinal characteristics of thoracic spinal nerve roots anomalies.

Purpose: The anomalous anatomical arrangement of the thoracic spinal nerve roots within the spinal canal can complicate the surgical treatment of several pathologies. The aim of this work was to reveal intraspinal anatomical variations of the thoracic spinal nerve roots.Methods: Anatomical study on 43 cadavers with a mean age of 53.7. After opening the spinal canal and dural sac, intradural and extradural anomalies of the thoracic spinal nerve roots were documented. Extradural communicating branches were excised, histologically processed and examined for the presence of nervous tissue.Results: We found 14 cases (32.6%) of intraspinal thoracic nerve root variations: intradural in 8 cases (18.6%), intradural communicating branches in 3 cases (6.97%), extradural anatomical variations occurred 6 cases (13.95%), 2 cases (4.65%) had extradural communicating branches between the nerve roots, 1 case had simultaneous occurrence of intradural and extradural communications (0.23%). All the results are differentiated according to the plexus type. In macroscopic extradural thoracic communicating branch had no nervous tissue on microscopy.Conclusions: This study describes intraspinal anatomical variations of thoracic spinal nerve roots. Knowledge of these variables should help prevent the failure of several medical procedures.

Extraordinary features of the intraspinal extradural and intradural nerve root courses.

OBJECTIVES: Very few studies have reported occasional intradural and extradural communications between adjacent nerve roots. These studies mostly focus on lumbosacral regions followed by cervical regions, and rarely in the thoracic region. DESIGN: The aim of this work is to point out some extraordinary extradural and intradural features of the intraspinal nerve root courses and their possible participation in radiculopathy. SUBJECTS AND METHODS: The anatomical study was performed in 43 cadavers. All intradural and extradural rami communicantes between nerve roots were examined histologically for the presence or absence of nervous tissue. RESULTS: Findings of the normotype of plexus formation occurred in 30 cases (69.8%). Variations in its formation were observed in 13 cases (30.2%). Anatomical preparations revealed intradural rami communicantes in all cases of the lumbosacral plexus; 28 times (65.1%) in cases of cervical roots and in the thoracic region 4 times (9.3%). Extradural anatomical variations occurred in 26 cases (60.5%). In 9 cases (20.9%) current occurence of intraspinal extradural and intradural communicating branches in the spinal canal were observed. Multiple extradural rami communicantes were observed in 6 cases (13.95%), including the simultaneous occurrence of multiple intradural and extradural ones in 5 cases (11.6%). CONCLUSIONS: This study allowed us to identify and describe current occurence of intraspinal extradural and intradural communicating branches in 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. The reliance of their incidence of the type of plexus was observed.

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.

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.

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.

Surgical location and anatomical variations of pudendal nerve.

BACKGROUND: An objective of our work was to clarify variations in pudendal nerve formation, as well as their possible impact on the clinical picture. METHOD: Bilateral pudendal nerve course and formation was studied on 20 adult cadavers. An anterior approach was used in 15 subjects, and both posterior and anterior approaches were used in five subjects. RESULTS: The prefixed type plexus formation was observed in eight cases (40%). In these cases, S(1) and S(2) roots contributed to the formation of the pudendal nerve. In the postfixed type, the S(3) root was dominant in two cases (66.7%), and less the S(4) root in one case (23.3%), albeit to a lesser degree. Most commonly, the S(2) root participated in its formation in 17 cases (85%). The inferior rectal nerve penetrating the sacrospinous ligament was seen in one case, arising from the pudendal nerve before entering the pudendal canal in four cases. The dorsal nerve of the penis arose from the S(1) root in two cases (10%). We observed it branching before entering the pudendal canal in 15 cases (75%), and it had divided in the pudendal canal in the other cases. For the posterior access, the pudendal nerve was localized 13.1 ± 0.72 cm medial to the greater trochanter, 8.1 ± 0.72 cm above the ischial tuberosity, at a depth of 6.4 ± 0.32 cm. CONCLUSIONS: This description may be useful when carrying out a pudendal nerve block and during surgical procedures carried out in this anatomical region.

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.

Anatomical variations of lumbosacral plexus.

BASIS: Deviations detected during spinal operations have motivated us to start research related to variations of lumbosacral plexus formation. Aim of this work was to find out deviations of its formation from ascension of particular roots from foramen invertebrale and foramina sacralia up to formation of terminal branches. SET: One hundred lumbosacral plexi have been examined in 50 adult cadavers for a purpose to find out an incidence of neural variations. We have observed participation of Th(12) root, L(4) and L(5) roots in its formation, as well as various deviations from ascension of particular plexiform roots up to their ending branches. For lumbal plexus, we have observed four nerve roots and six lumbal nerves; for sacral one, three sacral roots with a share of S(4) and lumbosacral trunk formed of L(4) and L(5) roots and four sacral nerves. We have considered also their course, anastomoses and thickness. We highlight motoric innervation particularities in relation to diagnostics besides anatomical complexity and variability. RESULTS: Variations on the level of neural roots were common, nerve formations were uncommon. Thickness of neural roots, formation or their absence were dependent on the type of plexus, particularly in sacral area. For lumbal plexus, L(1) root was the thinnest and L(4) root was the thickest. L(3) root was the thickest in six cases. Fifth lumbal root usually completely filled foramen invertebrale. We have observed double ascension of L(4) root from foramen invertebrale in 25 cases and plexiform in five cases. In other cases it was branched in various distance following ascension from foramen invertebrale. Plexiform ascension of L(3) root along with L(4) root was present in two cases. Double ascension of L(3) root was present in four cases. L(2), L(3) along with L(5) roots were doubled in two cases. Iliohypogastric nerve was the longest, ilioinguinal was the thinnest and nervus femoralis was the thickest. Changes in sacral plexus on the level of neural roots have been observed 41-times. Double ascension of L(5) root was present in eight cases and plexiform in four cases. Double S(1) root at ascension from foramina sacralia was present 16 times, S(2) 8 times, S(3) once and S(1) along with S(2) 4 times. S(1), S(2) and S(3) roots were branched in various distance following ascension from foramina sacralia in 15 cases. Truncus lumbosacralis was thickened in 19 cases, a share from L(4) root was thicker as L(5) root in 11 cases. Low level of connection between truncus lumbosacralis and S(1) root was observed in 10 cases. Nervus ischiadicus has branched into tibial and peroneal portions already in minor pelvis in two cases. The level of distance of n. (nervus) gluteus superior, n. gluteus inferior, n. cutaneus femoris posterior and n. pudendus was dependent on the plexus type. CONCLUSION: This study enabled us to find out and to describe extraordinary anatomical deviations in formation of neural roots and nerves of lumbal and sacral plexus, undescribed yet.

Variation of the median nerve course and its clinical importance.

AIMS AND METHODS: In our work we present and describe the variation of the course of the median nerve found in both upper limbs of one of the cadavers in our Institute of Anatomy (Medical Faculty, Comenius University, Bratislava, Slovakia) during the students' dissection of the peripheral nerves and vessels. RESULTS AND CONCLUSION: This non-standard course of the median nerve was compared with a standard course described in the anatomical literature and atlases, and confronted with the variations of the median nerve found and its course described in the available literature. We also provide some clinical implications of such peripheral nerve variability because understanding such anomalies is important in the diagnosis of unexplained clinical signs and symptoms as well as during nerve blocks and certain surgical procedures around the neck and proximal arm.

Peripheral nerve reconstruction by autograft.

The purpose of this retrospective clinical study was to present the results achieved by microsurgical reconstruction of peripheral nerve injuries in the 15 years between 1985 and 1999. Sixty patients underwent 63 surgical procedures. Forty-five nerves were reconstructed by autograft in 42 patients with injuries of the upper extremities; 14 patients had lower limb peripheral nerve reconstruction. The facial nerve was reconstructed by autograft in four patients. Factors that could possibly affect the results, such as delaying surgery, age of the patient, nature of the injury, length of the autograft, height of the injury and type of nerve damage, were assessed. The results were better in the reconstruction of nerve injuries in the upper than the lower limbs. Reconstruction of the tibial nerve was also rewarding. In general, the results of facial nerve reconstruction were good. The time between injury and reconstructive surgery was a crucial factor for successful outcome, especially in younger patients.