Background:The etiology of NPH is unknown, but might be related to altered craniospinal compliance caused by spinal canal narrowing, as has been suggested by in-vitro simulation studies. However, clinical evidence is lacking. We explored associations between cervical (CS) and lumbar (LS) spinal stenoses, and NPH-imaging characteristics. Methods:Spinal MRI of NPH-patients scheduled for shunt-surgery was retrospectively evaluated by measuring the minimal dural sac cross-sectional area (DSCSA), and anterior-posterior diameter (AP) in CS and LS. Cranial-CT was evaluated regarding Evans-Index, callosal angle (CA), and Radscale-Score. CS and LS were each sub-grouped by median split into small/large DSCSA and small/large AP, and CT-parameters compared using Mann-Whitney-U-Tests, tested one-sided (p < .05, Bonferroni-Holm-corrected for multiple comparisons p Holm). Partial correlations were explored between stenoses- and cranial-imaging parameters. Results:Out of 426 NPH-patients screened, 114 patients had spinal-MRI. Of those with cervical-MRI (n = 100), 90% had CS, of those with lumbar-MRI (n = 86), 71% had LS. Among these, 60 patients had cervical and lumbar MRI, of which 63% showed combined CS and LS. CA was larger in CS patients with small as compared to large AP (p = .045, r = .235, 95%CI [.002, .444]), and in LS patients with small as compared to large DSCSA (p = .022, r = .330, 95%CI [.060, .555]), which did however not remain significant after correction for multiple comparisons (p Holm> .05). Lumbar AP tended to be negatively correlated to the Radscale-Score (p = .041, r = -0.31, 95%CI [-.561,-.014], p Holm> .05). Conclusions:Spinal stenosis might be associated with NPH-related imaging characteristics. Prospective studies should investigate the potential pathophysiological impact of degenerative spine-disease on NPH.

Conventional navigation systems (CNS) in surgery require strong spatial cognitive abilities and hand-eye coordination. Augmented Reality Navigation Systems (ARNS) provide 3D guidance and may overcome these challenges, but their accuracy and efficiency compared to CNS have not been systematically evaluated. In this randomized crossover study with 36 participants from different professional backgrounds (surgeons, students, engineers), drilling accuracy, time and perceived workload were evaluated using ARNS and CNS. For the first time, this study provides compelling evidence that ARNS and CNS have comparable accuracy in translational error. Differences in angle and depth error with ARNS were likely due to limited stereoscopic vision, hardware limitations, and design. Despite this, ARNS was preferred by most participants, including surgeons with prior navigation experience, and demonstrated a significantly better overall user experience. Depending on accuracy requirements, ARNS could serve as a viable alternative to CNS for guided drilling, with potential for future optimization.

OBJECTIVE This study evaluates the precision of a commercially available spine planning software in automatic spine labelling and screw-trajectory proposal. METHODS The software uses automatic segmentation and registration of the vertebra to generate screw proposals. 877 trajectories were compared. Four neurosurgeons assessed suggested trajectories, performed corrections, and manually planned pedicle screws. Additionally, automatic identification/labelling was evaluated. RESULTS Automatic labelling was correct in 89% of the cases. 92.9% of automatically planned trajectories were in accordance with G&R grade A + B. Automatic mode reduced the time spent planning screw trajectories by 7 s per screw to 20 s per vertebra. Manual mode yielded differences in screw-length between surgeons (largest distribution peak: 5 mm), automatic in contrast at 0 mm. The size of suggested pedicle screws was significantly smaller (largest peaks in difference between 0.5 and 3 mm) than the surgeon's choice. CONCLUSION Automatic identification of vertebrae works in most cases and suggested pedicle screw trajectories are acceptable. So far, it does not substitute for an experienced surgeon's assessment.

PURPOSE:Instrumentation in spinal revision surgery is considered challenging. Altered or missing anatomical landmarks hinder the surgeons' intraoperative orientation. In recent history, the importance of navigated approaches to spinal screw placement is constantly increasing. A growing number of medical centers have introduced intraoperative CT (iCT) navigation as a new clinical standard. In this study, we compare the accuracy of dorsal iCT-navigated instrumentation in revision surgery versus primary interventions.METHODS:Between September 2017 and January 2019, we prospectively analyzed a consecutive series of dorsal instrumentation using iCT. Patients with previous operative interventions in the relevant spinal segments were included in the revision group and compared with a previously assessed group of primary interventions (nonrevision group). Each screw was assessed individually by an independent observer, making use of a modified Gertzbein and Robbins classification.RESULTS:In this period, 39 patients were treated in the revision group with a total amount of 269 implanted screws. We achieved an overall accuracy of 95.91% compared with 95.12% in the nonrevision group (46 patients, 287 screws). We found no significant difference in accuracy between the two groups or any anatomical region of the spine.CONCLUSION:In summary, iCT-navigated screw placement yields a good accuracy in spinal revision surgery, without significant difference to primary interventions.

Accurate planning transfer is a prerequisite for successful operative care. For different applications, diverse computer-assisted systems have been developed and clinically evaluated. This paper presents the implementation and evaluation of a new modular concept. The approach is based on passive application specific kinematics that are semi-automatically adjusted using a universal hand-held computer controlled Smart Screw Driver. The system was realized for pedicle screw instrumentation and evaluated according to IEC 60601-1-6 (usability engineering). The accuracies of the drill holes achieved were comparable with robotic approaches, while operation time and radiation were reduced compared with conventional operation techniques. The adjustment procedure has proven high learnability and user satisfaction. The next step will be optimization of the kinematic structure and fixation to the patient in order to increase accuracies of planning transfer as well as evaluation of the overall system by medical staff in preclinical and clinical studies.

The aim of this work was to determine predictors that may contribute to surgical success or failure. Relevant pre- and postoperative baseline data were analyzed, and temporal structures underwent a volumetric analysis.

Background It is not known whether following transsphenoidal surgery for pituitary adenomas the vision of patients with preoperative chiasma syndromes (CS) does improve to the degree of vision of patients without preoperative CS. Objective The purpose of this study is to answer the question above. Methods Pertinent data of a successive series of patients operated transsphenoidally for the first time for pituitary adenoma were retrospectively analysed. Results Of the 304 patients, 35.1% presented preoperatively with CS. The median visual acuity (VA) of these patients improved significantly from preoperative (right eye, 0.63 (0; 1.25); left eye, 0.56 (0; 1.4)) to postoperative (right eye, 0.8 (0; 1.25); left eye, 0.74 (0; 1.25)). The median number of impaired quadrants of the binocular visual fields (VF) improved significantly from preoperative (2 (0; 8)) to postoperative CS (0 (0; 4)). In patients without preoperative CS, postoperative vision (VA as well as VF) remained unchanged. Postoperatively, VA of patients with preoperative CS remained significantly lower than that of patients without preoperative CS (right eye, 0.96 (0.2; 1.4); left eye, 0.94 (0.05; 1.4)). Postoperatively, the number of impaired quadrants of the binocular VF of patients with preoperative CS remained significantly higher than in patients without preoperative CS (0 (0; 1)). Conclusion In this unselected patient series, the vision (VA as well as VF) of patients with preoperative CS did not improved postoperatively to the degree of the vision of patients without preoperative CS. Thus, in patients with adenomatous chiasma compression transsphenoidal surgery may be indicated before CS develops.

The purpose of this study was to report on the incidence, diagnosis and clinical manifestation of VAI following cervical spine injuries observed in a prospective observational study with a standardized clinical and radiographical protocol.

To describe the functional impairment caused by chiasma syndromes (CS) prior to and following transsphenoidal pituitary adenoma surgery.

The objective of the study was to describe the technique, accuracy of placement and complications of transpedicular C2 screw fixation without spinal navigation. Patients treated by C2 pedicle screw fixations were identified from the surgical log book of the department. Clinical data were extracted retrospectively from the patients' charts. Pedicle screw placement accuracy was assessed on postoperative CT scans according to Gertzbein and Robbins (GRGr). A total of 27 patients were included in the study. The mean age of the patients was 56 +/- 22.0 years; 51.9% of them were female. As much as 17 patients suffered from trauma, 5 of degenerative disease, 3 of inflammations and 2 of metastatic disease. A total of 47 C2 transpedicular screw fixations were performed. The canulated screws were inserted under visual control following the preparation of the superior surface of the isthmus and of the medial surface of the pedicles of the C2. Intraoperative fluoroscopy was additionally used. The postoperative CT findings showed in 55.3% GRGr 1, in 27.7% GRGr 2, in 10.6% GRGr 3, and in 6.3% GRGr 4 pedicle screw insertion accuracy. Screw insertions GRGr 5 were not observed. Screw malpositioning (i.e., GRGr 3 and 4) was significantly associated with thin (<5 mm) pedicle diameters and with surgery for C2 fractures. In the three patients with screw insertions GRGr 4, postoperative angiographies were performed to exclude vertebral artery affections. In one of these three cases, the screw caused a clinically asymptomatic vertebral artery compression. Hardware failures did not occur. In one patient, postoperative pneumonia resulted in the death of the patient. Careful patient selection and surgical technique is necessary to avoid vertebral artery injury in C2 pedicle screw fixation without spinal navigation. A slight opening of the vertebral artery canal (Gertzbein and Robbins grade < or =3) does not seem to put the artery at risk. However, the high rate of misplaced screws when inserted without spinal navigation, despite the fact that no neurovascular injury occurred, supports the use of spinal navigation in C2 pedicle screw insertions.

The objective of the article is to verify the hypothesis that the dorsal multilevel laminectomy and rod-screw-instrumented fusion (DLF) for multilevel spondylotic cervical myelopathy (MSCM) is less strenuous for patients, and less prone to perioperative complications, than ventral multilevel corpectomy and plate-screw-instrumented fusion (VCF), while clinical outcome is comparable. One hundred and three successive patients were treated for at least two vertebral-level MSCM, 42 of them by VCF and 61 by DLF. The two patients groups were retrospectively compared. VCF patients were slightly younger than DLF patients (62.5 ± 10.61 years versus 66 ± 12.4 years, P = 0.012). In VCF patients, a median of 2 (2–3) corpectomies and in DLF patients a median of 3 (2–5) laminectomies were performed. In VCF patients, surgery lasted longer than in DLF patients (229 ± 60 min versus 183 ± 46 min, P ≤ 0.001). Between the VCF and the DLF patients groups, no significant difference was found in perioperative complications (e.g. hardware failure rates of 16.7% in VCF and of 6.6% in the DLF patients) and mortality rates. The postoperative outcome, as assessed by the postoperative change of the Nurick scores, the change of neck pain, the patients' satisfaction, and the change of the subaxial Cobb angle of the spine did not differ between the two patients groups. However, when comparing the postoperative Nurick scores directly, VCF patients fared somewhat better than DLF patients [median of 2 (0–5) versus 3 (1–5), P = 0.003]. The hypothesized advantages of DLF over VCF in the surgical treatment of at least two vertebral-level MSCM could not be confirmed in this retrospective study. A prospective randomized study is warranted to clarify this issue.

The aim of this study was to investigate the influence of the postoperative hippocampal remnant on postoperative seizure and neuropsychological outcome in temporal lobe epilepsy (TLE). Postoperative volumetric MRI measurements of 53 patients surgically treated for TLE revealed a postoperative volume loss of the hippocampal remnant compared with the respective preoperative segment in all patients. Extent of preoperative hippocampal pathology, remnant shrinkage, resection volume, and postoperative volume of the hippocampal remnant did not correlate with seizure outcome 1 year after surgery. With respect to neuropsychological outcome, performance on tasks assessing verbal memory and language-related functions was impaired in patients with left-sided pathology after surgery. Performance of patients with right-sided pathology (n=26) demonstrated no significant correlation with hippocampal measures or with neuropsychological data. Degree of hippocampal remnant shrinkage seems to be associated with decreased verbal memory performance in patients with left-sided TLE.

Since magnetic resonance imaging (MRI) technique is constantly evolving with higher field strength scanners, the question arises whether images from different field strength scanners can be used interchangeably for scientific and clinical purposes. We address this issue in a study group of patients with temporal lobe epilepsy (TLE). Two different quantification methods for analysing structural (MRI) were used. Conventional volumetry was performed by manually tracing amygdala and hippocampus volumes on both 1.5 and 3 T scans of 10 TLE patients. Additionally a voxel-based morphometry (VBM)-based extraction of those structures was conducted. As an answer to the main question, it was determined that the volumetrically derived volumes of amygdala and hippocampus from 1.5 and 3.0 T images did not differ. Our findings concerning the volumetry are consistent with findings in healthy controls, thus offering the possibility to use volumetry of the different scanners interchangeably. The results of the VBM-analyses show satisfying inter-scanner volume quantification but not consistent enough to be deemed interchangeable. Further investigations analysing the outcomes of conventional VBM of different field strength scanners are necessary.

INTRODUCTION:The aim of this study was to test a modified radial semiautomated volumetry technique (radial divider technique, RDT) versus the manual volumetry technique (MVT) for proportionality of temporal subvolumes in 30 patients with drug-resistant temporal lobe epilepsy.METHODS:Included in the study were 30 patients (15 female, 15 male; mean age 39.6 years) with pharmacoresistant epilepsy (mean duration 26.6 years). MRI studies were performed preoperatively on a 1.5-T scanner. All image processing steps and volume measurements were performed using ANALYZE software. The volumes of six subregions were measured bilaterally; these included the superior temporal gyrus (STG), middle + inferior temporal gyrus (MITG), fusiform gyrus (FG), parahippocampal gyrus (PHG), amygdala (AM), and hippocampus (HP). Linear regression was used to investigate the relationship between the comparable subvolumes obtained with MVT and RDT.RESULTS:Very high correlations (R (2) >0.95) between RDT and MVT were observed for the STG + MITG and the STG + MITG + FG, but low correlations for the PHG subvolumes and the combined PHG + HP + AM subvolumes. These observations were independent of the side of the pathology and of hemisphere.CONCLUSION:The two measurement techniques provided highly reliable proportional results. This series in a homogeneous group of TLE patients suggests that the much quicker RDT is suitable for determining the volume of temporolateral and laterobasal temporal lobe compartments, of both the affected and the non-affected side and the right and left hemisphere.

Object. Spinal cord injury (SCI) induces the disruption of neural and vascular structures. In contrast to the emerging knowledge of mechanisms regulating the onset of the postinjury angiogenic response, little is known about counterregulatory signals. Methods. Using immunohistochemical methods, the authors investigated the expression of the endogenous angiogenic inhibitor endostatin/collagen XVIII during the tissue remodeling response to SCI. Results. After SCI, endostatin/collagen XVIII + cells accumulated at the lesion site, in pannecrotic regions (especially in areas of cavity formation), at the lesion margin/areas of ongoing secondary damage, and in perivascular Virchow–Robin spaces. In remote areas (> 0.75 cm from the epicenter) a more modest accumulation of endostatin/collagen XVIII + cells was observed, especially in areas of pronounced Wallerian degeneration. The numbers of endostatin/collagen XVIII + cells reached their maximum on Day 7 after SCI. The cell numbers remained elevated in both, the lesion and remote regions, compared with control spinal cords for 4 weeks afterwards. In addition to being predominantly confined to ED1 + -activated microglia/macrophages within the pannecrotic lesion core, endostatin/collagen XVIII expression was frequently detected by the endothelium/vessel walls. Numbers of lesional endostatin/collagen XVIII + endothelium/vessel walls were found to increase early by Day 1 postinjury, reaching their maximum on Day 3 and declining subsequently to enhanced (above control) levels 30 days after SCI. Conclusions. The authors detected that in comparison to the early expression of neoangiogenic factors, there was a postponed lesional expression of the antiangiogenic endostatin/collagen XVIII. Furthermore, the expression of endostatin/collagen XVIII was localized to areas of neovascular pruning and retraction (cavity formation). The expression of endostatin/collagen XVIII by macrophages in a “late” activated phagocytic mode suggests that this factor plays a role in counteracting the preceding “early” neoangiogenic response after SCI.

We have analysed the expression of the endogenous angiogenesis inhibitor endostatin/collagen XVIII following stab wound injury and observed a highly significant (p < 0.0001) lesional accumulation confined to areas of pan-necrotic injury and developing secondary damage. Maximal cell numbers were detected at Day 14, declining until Day 21 after injury. Further, endostatin/collagen XVIII+ monocytic cells accumulated in Virchow–Robin spaces where they formed cell clusters. Besides being prevailingly localised to ED1+ activated microglia/macrophages, endostatin/collagen XVIII expression was also detected by subendothelial surrounding vessels in the lesioned area. Late and prolonged accumulation of endostatin/collagen XVIII+ microglia/macrophages and increased numbers of endostatin/collagen XVIII+ subendothelial cells/vessels in areas of vascular pruning and regression, point to a role in the termination of the transient angiogenic response, linked to a "late" inflammatory milieu.

In this study, we describe a differential mass spectrometric technique for the immuno-proteomic analysis of the major histocompatibility complex (MHC) peptides of a renal cell carcinoma (RCC) biopsy compared with the healthy kidney tissue of the same patient after nephrectomy. Using a stable isotope labeling approach, we could directly compare and relatively quantify 43 MHC-peptide pairs, most of which were present in similar proportions on both normal kidney and tumor. Significantly, two dominant peptides of monoisotopic masses ([M+H](+)) 973.43 u and 967.59 u, respectively, were found exclusively in the tumor sample. One of these was identified as originating from heme oxygenase-1 (HO-1), a protein involved in induction of apoptosis resistance, immunosuppression andneoangiogenesis and reported to be up-regulated in various cancer types. Moreover, the corresponding synthetic HO-1-derived peptide was shown to be immunogenic in vitro by generation of CD8(+) T cell lines with peptide-specific cytolytic activity. Thus, this peptide is an example of a differentially identified T cell epitope that could be considered as a target for immunotherapy.

OBJECT Spinal cord injury (SCI) elicits a strong inflammatory response that readily participates in lipid oxygenation, edema formation, apoptotic cell death, and tissue remodeling. Because cytokines determine the postinjury inflammatory milieu, the authors analyzed the expression of the immunomodulatory chemokine interleukin- 16 (IL- 16) after SCI. METHODS The authors detected a highly significant, persistent, lesional accumulation of parenchymal IL-16+ microglia/macrophages, which reached a maximal level 3 days postinjury compared with control rats. The majority of cells that demonstrated positive labeling for IL-16 also had positive labeling for ED1 (> 70%) and OX-8/CD8; these cells exhibited the morphological hallmarks of activated microglia/macrophages and pronounced MHC Class II expression. In contrast to IL-16+ED1+ cells, IL-16+ microglia/macrophages that coexpressed OX-8 were exclusively seen in the pannecrotic lesion core. In addition, clustering of IL-16+ cells was observed in perivascular Virchow-Robin-like spaces in areas of the primary injury (lesion core) and in immediately adjacent areas of secondary injury. Furthermore, on Day 3 postinjury, IL-16+ microglia/macrophages were frequently observed in a perineuronal position. CONCLUSIONS The early lesional accumulation of IL-16+ microglia/macrophages suggests a role for IL-16 in the early postinjury immune response such as recruitment and activation of immune cells, leading to microvessel clustering and secondary damage progression.

The protein pattern of healthy human eccrine sweat was investigated and 10 major proteins were detected from which apolipoprotein D, lipophilin B, and cathepsin D ( CatD) were identified for the first time in human eccrine sweat. We focused our studies on the function of the aspartate protease CatD in sweat. In vitro digestion experiments using a specific fluorescent CatD substrate showed that CatD is enzymatically active in human sweat. To identify potential substrates of CatD in human eccrine sweat LL-37 and DCD-1L, two antimicrobial peptides present in sweat, were digested in vitro with purified CatD. LL-37 was not significantly digested by CatD, whereas DCD-1L was cleaved between Leu(44) and Asp(45) and between Leu(29) and Glu(30) almost completely. The DCD-1L-derived peptides generated in vitro by CatD were also found in vivo in human sweat as determined by surface-enhanced laser desorption/ ionization (SELDI) mass spectrometry. Furthermore, besides the CatD-processed peptides we identified additionally DCD-1L-derived peptides that are generated upon cleavage with a 1,10-phenanthroline- sensitive carboxypeptidase and an endoprotease. Taken together, proteolytic processing generates 12 DCD-1L-derived peptides. To elucidate the functional significance of postsecretory processing the antimicrobial activity of three CatD-processed DCD-1L peptides was tested. Whereas two of these peptides showed no activity against Gram-positive and Gram-negative bacteria, one DCD-1L-derived peptide showed an even higher activity against Escherichia coli than DCD-1L. Functional analysis indicated that proteolytic processing of DCD-1L by CatD in human sweat modulates the innate immune defense of human skin.

The search for novel molecular markers of tumor invasion is vital if strategies are to become more effective in the diagnostic and prognostic management of transitional cell carcinoma of the bladder. Up to 50% of tumors detected at stage 1 (pT1) progress to a higher grade even after endoscopic surgical resection, and there are currently no protein markers of this aggressive, invasive phenotype. We have combined SELDI-TOF-MS, ClinProt magnetic bead enrichment, Nano-LC-ESI-ion trap tandem mass spectrometry and immunohistochemical analysis to the study of 12 invasive bladder cancer tissue biopsies paired with normal bladder tissue samples obtained from the same patients for the definition and identification of proteins up-regulated in the tumors. We report the inflammation-associated calcium binding protein S100A8 (MRP-8, calgranulin A) to be highly expressed in tumor cells in contrast to normal urothelium in 50% of the samples, as well as two unidentified protein markers at 5.75 and 6.89 kDa that were differentially detected in 9/12 and 10/ 12 tumor samples, respectively. These new markers, when fully characterized, may contribute to new target proteins for the prediction of aggressive, invasive bladder tumors.