Treatment bias was demonstrated regarding resection and second-line therapies. However, bias and imbalances were controllable in the cohorts available from the 5-aminolevulinic acid study so that the present data now provide Level 2b evidence (Oxford Centre for Evidence-based Medicine) that survival depends on complete resection of enhancing tumor in glioblastoma multiforme.

In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue. How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical. Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen availability and tissue damage.

Robotic-guided and percutaneous pedicle screw placement are emerging technologies. We here report a retrospective cohort analysis comparing conventional open to open robotic-guided and percutaneous robotic-guided pedicle screw placement. 112 patient records and CT scans were analyzed concerning the intraoperative and perioperative course. 35 patients underwent percutaneous, 20 open robotic-guided and 57 open conventional pedicle screw placement. 94.5% of robot-assisted and 91.4% of conventionally placed screws were found to be accurate. Percutaneous robotic and open robotic-guided subgroups did not differ obviously. Average X-ray exposure per screw was 34 s in robotic-guided compared to 77 s in conventional cases. Subgroup analysis indicates that percutaneously operated patients required less opioids, had a shorter hospitalization and lower rate of adverse events in the perioperative period. The use of robotic guidance significantly increased accuracy of screw positioning while reducing the X-ray exposure. Patients seem to have a better perioperative course following percutaneous procedures.

After aneurysmal subarachnoid hemorrhage (SAH), patients frequently present with persistent bodily, psychosocial, and cognitive impairments that resemble those of patients with untreated partial or complete pituitary insufficiency. Because of these similarities, the authors hypothesized that aneurysmal SAH may cause pituitary dysfunction. Pituitary function testing was performed in 40 aneurysmal SAH patients between 12 and 72 months after the SAH. A combined TRH-LHRH-arginine test and the insulin tolerance test were performed on two separate days. Only 18 of 40 (45%) of the tested patients had normal pituitary function. Five of 40 exhibited isolated severe GH deficiency (GHD), and an additional three of 40 had severe GHD plus corticotroph deficiency. Isolated corticotroph deficiency was seen in 13 of 40 patients, and one patient showed isolated thyrotroph deficiency. All but one patient with corticotroph insufficiency were female. Patients with severe GHD had gained significantly more weight since their SAH than patients without GHD and exhibited a significantly higher body mass index. None of the clinical parameters indicative of a poor neurological outcome in aneurysmal SAH were related to pituitary insufficiency. In summary, neuroendocrine dysfunction was identified in a substantial portion of patients with previous aneurysmal SAH and should be borne in mind as a potential long-term sequel of the illness.

The rate of complications in patients with cSDH who underwent the BCD is high. The clinical relevance of medical complications has to be emphasized because of their substantial contribution to overall mortality.

Glioblastoma multiforme (GBM) is the most frequent and devastating primary brain tumor in adults. The presence of epigenetic lesions, like hypermethylation of known tumor suppressor genes such as MGMT, has been widely described in GBM, but to our knowledge, a genome-wide profile of DNA methylation changes in these lethal tumors is not yet available. In the present analysis, we have quantified the DNA methylation level of 1,505 CpG dinucleotides (807 genes) in 87 consecutive GBMs using universal BeadArrays. Supervised cluster analyses identified 25 and seven genes that were respectively hypermethylated and hypomethylated in more than 20% of the cases studied. The most frequently hypermethylated genes were HOXA11, CD81, PRKCDBP, TES, MEST, TNFRSF10A and FZD9, being involved in more than half of the cases. Studying the biological features of hypermethylated genes, we found that the group of genes hypermethylated in GBM was highly enriched (41%, p < 0.001) for targets of the PRC2 (Polycomb repressive complex 2) in embryonic stem cells. This suggests that GBM might be derived from precursor cells with stem cell-like features. DNA methylation profiles were associated with overall survival in GBM, and we confirmed the favorable prognostic impact of MGMT methylation in patients treated with alkylating agents. Furthermore, we identified that promoter hypermethylation of the transcription factor gene GATA6 (occurring in 30% of GBM) was significantly associated with unfavorable patient survival.

BACKGROUND AND PURPOSE:Autoimmune hypophysitis (AH) mimics the more common nonsecreting pituitary adenomas and can be diagnosed with certainty only histologically. Approximately 40% of patients with AH are still misdiagnosed as having pituitary macroadenoma and undergo unnecessary surgery. MR imaging is currently the best noninvasive diagnostic tool to differentiate AH from nonsecreting adenomas, though no single radiologic sign is diagnostically accurate. The purpose of this study was to develop a scoring system that summarizes numerous MR imaging signs to increase the probability of diagnosing AH before surgery.

OBJECTIVEThe quest to improve the safety and accuracy and decrease the invasiveness of pedicle screw placement in spine surgery has led to a markedly increased interest in robotic technology. The SpineAssist from Mazor is one of the most widely distributed robotic systems. The aim of this study was to compare the accuracy of robot-guided and conventional freehand fluoroscopy-guided pedicle screw placement in thoracolumbar surgery.METHODSThis study is a retrospective series of 169 patients (83 women [49%]) who underwent placement of pedicle screw instrumentation from 2007 to 2015 in 2 reference centers. Pathological entities included degenerative disorders, tumors, and traumatic cases. In the robot-assisted cohort (98 patients, 439 screws), pedicle screws were inserted with robotic assistance. In the freehand fluoroscopy-guided cohort (71 patients, 441 screws), screws were inserted using anatomical landmarks and lateral fluoroscopic guidance. Patients treated before 2009 were included in the fluoroscopy cohort, whereas those treated since mid-2009 (when the robot was acquired) were included in the robot cohort. Since then, the decision to operate using robotic assistance or conventional freehand technique has been based on surgeon preference and logistics. The accuracy of screw placement was assessed based on the Gertzbein-Robbins scale by a neuroradiologist blinded to treatment group. The radiological slice with the largest visible deviation from the pedicle was chosen for grading. A pedicle breach of 2 mm or less was deemed acceptable (Grades A and B) while deviations greater than 2 mm (Grades C, D, and E) were classified as misplacements.RESULTSIn the robot-assisted cohort, a perfect trajectory (Grade A) was observed for 366 screws (83.4%). The remaining screws were Grades B (n = 44 [10%]), C (n = 15 [3.4%]), D (n = 8 [1.8%]), and E (n = 6 [1.4%]). In the fluoroscopy-guided group, a completely intrapedicular course graded as A was found in 76% (n = 335). The remaining screws were Grades B (n = 57 [12.9%]), C (n = 29 [6.6%]), D (n = 12 [2.7%]), and E (n = 8 [1.8%]). The proportion of non-misplaced screws (corresponding to Gertzbein-Robbins Grades A and B) was higher in the robot-assisted group (93.4%) than the freehand fluoroscopy group (88.9%) (p = 0.005).CONCLUSIONSThe authors’ retrospective case review found that robot-guided pedicle screw placement is a safe, useful, and potentially more accurate alternative to the conventional freehand technique for the placement of thoracolumbar spinal instrumentation.