Riscurile și beneficiile înregistrării cu microelectrod în chirurgia bolii Parkinson

Background. Microelectrode recording is believed to improve the outcome by enhancing the precision of electrodes used in deep brain stimulation in patients with Parkinson’s Disease. There is a trend that higher number of penetrations correlate with high rate of hemorrhagic complications. Objective of the study. Determine the clinical outcome of patients stimulated decentrally compared to those placed centrally. Additionally, to assess whether a higher number of penetrations correlate with higher rates of intracranial bleeding. Material and Methods. This monocentric study included 556 patients with bilateral STN-DBS and relies on a large prospectively established database. Data were available from 400 patients. The outcome parameter was the stimulation-induced improvement of the UPDRS for PD. We compared patients with both electrodes centrally to that bi-decentrally. Also, we determined the rate of surgical complications. Results. A decentral tract was chosen in 41% of the electrodes based on clinical grounds (central, n = 471 electrodes; decentral, n = 329). Motor symptom improvement was not different between patients with electrodes implanted bilaterally in the central (44.39% ± 22.71) or decentral (43,22% ± 17) trajectory bilaterally (p = 0.5571). Similar results were obtained for the hemibody score and subscores for akinesia, tremor, rigidity, postural instability and gait disorder. The overall bleeding rate was 2,78% and not depending on the number of penetrations. Conclusion. Outcomes between the groups with central or decentral electrode trajectories did not differ and, therefore, the use of mMER is likely to improve outcome quality. Comparison with other cohorts does not disclose a higher rate of bleeding complications in this cohort with mMER. Introducere. În chirurgia bolii Parkinson, înregistrarea cu microelectrod se utilizează pentru determinarea punctului optim pentru stimulare cerebrală profundă. Se consideră că numărul crescut de penetrații corelează cu rata mai mare a complicațiilor hemoragice postoperatorii. Scopul lucrării. De a determina efectul clinic al pacienților stimulați cu electrozi bicentral versus cei implantați decentral bilateral. De asemenea, de a evalua dacă numărul mai mare de penetrații corelează cu rata mai mare a sângerării intracraniene. Material și Metode. Acest studiu monocentric a inclus 556 de pacienți cu boala Parkinson, stimulați bilateral, bază pe o bază de date prospectivă. Datele complete au fost găsite la 400 de pacienți. Parametrul pentru comparație a fost scala UPDRS pentru BP. Studiul nostru a comparat pacienții cu ambii electrozi implantați bilateral central și decentral. De asemenea, s-a studiat rata sângerării postoperatorii. Rezultate. Traiectorie decentrală s-a ales în 41% din electrozi pe baza la rezultatul clinic (central - 471 electrozi, decentral - 329). Ameliorarea simptomelor motorii nu diferă între grupurile de pacienți cu electrozi implantați bilateral central (44.39% ± 22.71) sau decentral (43, 22% ± 17), p = 0.56. Aceleași rezultate s-au obținut pentru scorul hemibody și subscoruri ca: akinezia, tremorul, rigiditatea, tulburările de statică și mers. Incidența hemoragiei a fost de 2.78% și nu corelează cu numărul de penetrații cu microelectroade. Concluzii. Rezultatul clinic al pacienților cu ambii electrozi bilateral central și decentral nu diferă. Astfel, utilizarea MER poate ameliora rezultatul final. Totodată, incidența complicațiilor postoperatorii hemoragice în studiul nostru nu este mai mare decât în alte studii

Evaluation of a Brown Seaweed Extract from Dictyosiphon foeniculaceus as a Potential Therapeutic Agent for the Treatment of Glioblastoma and Uveal Melanoma

Ingredients of brown seaweed like fucoidans are often described for their beneficial biological effects, that might be interesting for a medical application. In this study, we tested an extract from Dictyosiphon foeniculaceus (DF) to evaluate the effects in glioblastoma and uveal melanoma, looking for a possible anti-cancer treatment. We investigated toxicity, VEGF (vascular endothelial growth factor) secretion and gene expression of tumor and non-tumor cells. SVGA (human fetal astrocytes), the human RPE (retinal pigment epithelium) cell line ARPE-19, the tumor cell line OMM-1 (human uveal melanoma), and two different human primary glioblastoma cultures (116-14 and 118-14) were used. Tests for cell viability were conducted with MTS-Assay (3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), and the proliferation rate was determined with cell counting. VEGF secretion was assessed with ELISA (enzyme-linked immunosorbent assay). The gene expression of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2) and VEGF-A was determined with real-time qPCR (quantitative polymerase chain reaction). DF lowered the cell viability of OMM-1. Proliferation rates of ARPE-19 and OMM-1 were decreased. The VEGF secretion was inhibited in ARPE-19 and OMM-1, whereas it was increased in SVGA and 116-14. The expression of VEGFR1 was absent and not influenced in OMM-1 and ARPE-19. VEGFR2 expression was lowered in 116-14 after 24 h, whereas VEGF-A was increased in 118-14 after 72 h. The extract lowered cell viability slightly and was anti-proliferative depending on the cell type investigated. VEGF was heterogeneously affected. The results in glioblastoma were not promising, but the anti-tumor properties in OMM-1 could make them interesting for further research concerning cancer diseases in the human eye

Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells

Glioblastoma cells with stem-like properties control brain tumour growth and recurrence. Here, we show that endogenous neural precursor cells perform an anti-tumour response by specifically targeting stem-like brain tumour cells. In vitro, neural precursor cells predominantly express bone morphogenetic protein-7; bone morphogenetic protein-7 is constitutively released from neurospheres and induces canonical bone morphogenetic protein signalling in stem-like glioblastoma cells. Exposure of human and murine stem-like brain tumour cells to neurosphere-derived bone morphogenetic protein-7 induces tumour stem cell differentiation, attenuates stem-like marker expression and reduces self-renewal and the ability for tumour initiation. Neurosphere-derived or recombinant bone morphogenetic protein-7 reduces glioblastoma expansion from stem-like cells by down-regulating the transcription factor Olig2. In vivo, large numbers of bone morphogenetic protein-7-expressing neural precursors encircle brain tumours in young mice, induce canonical bone morphogenetic protein signalling in stem-like glioblastoma cells and can thereby attenuate tumour formation. This anti-tumour response is strongly reduced in older mice. Our results indicate that endogenous neural precursor cells protect the young brain from glioblastoma by releasing bone morphogenetic protein-7, which acts as a paracrine tumour suppressor that represses proliferation, self-renewal and tumour-initiation of stem-like glioblastoma cell

The role of microelectrode recording during Deep Brain Stimulation of Subthalamic Nucleus in patients with Parkinson’s disease

Background: Deep brain stimulation of the subthalamic nucleus improves symptoms of Parkinson’s disease. However, the clinical outcome depends on the accurate location of the final electrode. Multiple microelectrode recording is believed to improve the precision, although it prolongs the duration of surgery. We hypothesize that patients implanted in the central trajectory have the same outcome as patients implanted decentrally. Material and methods: This study was carried out in UKSH Kiel and included 556 patients treated from 1999 until 2018 with bilateral STN-DBS (safety population). Pre- and postoperative efficacy data were available from 400 patients. The outcome parameter was the stimulation-induced improvement of the UPDRS for PD. We compared patients with both electrodes centrally to that bi-decentrally. The rate of surgical complications was determined with postoperative imaging. Results: A decentral tract was chosen in 41% of the electrodes (central, n = 471 electrodes; decentral, n = 329). Motor improvement was not different between patients with electrodes implanted bicentral (44.39% ± 22.71) or decentral (43.22% ± 17) trajectory bilaterally (p = 0.5571). Similar results were obtained for the hemi body score and subscores for akinesia, tremor, rigidity, postural instability and gait disorder. The overall bleeding rate was 2.78% and not dependent on the number of penetrations. Conclusions: Outcomes between the groups did not differ and, therefore, the use of mMER is likely to improve the outcome. Comparison with other cohorts does not disclose a higher rate of bleeding complications in this cohort with mMER

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

Role of neurotransmitter receptors and neural progenitors in glioma brain parenchyma interaction

Hirneigene Tumor wie die Gruppe der Gliome sind bisher wenig in ihrer Interaktion mit dem Hirnparenchym untersucht. In dieser Arbeit werden sowohl zelluläre als auch humorale Mechamismen in der Interaktionen von Gliomen untersucht. Dabei kann die besondere Rolle der immunkompetenten Zelle des ZNS, der Mikroglia, als auch der endogener neuronaler Vorläuferzellen herausgearbeitet werden.Interaction of primary brain tumors like glioma with brain parenchyma are not investigated in detail yet. Here the cellular and humoral mechanisms of glioma-parenchyma-interaction are explored and the highlighted role of microglia and endogenous neural progenitors are delinated

Intraoperative resection control using arterial spin labeling — Proof of concept, reproducibility of data and initial results

Objectives: Intraoperative magnetic resonance imaging is a unique tool for visualizing structures during resection and/or for updating any kind of neuronavigation that might be hampered as a result of brain shift during surgery. Advanced MRI techniques such as perfusion-weighted imaging have already proven to be important in the initial diagnosis preoperatively, but can also help to differentiate between tumor and surgically induced changes intraoperatively. Commonly used methods to visualize brain perfusion include contrast agent administration and are therefore somewhat limited. One method that uses blood as an internal contrast medium is arterial spin labeling (ASL), which might represent an attractive alternative. Materials and methods: Ten healthy volunteers were examined using three different scanners and coils within 1h (3T Achieva MRI using 32-channel head coil, 1.5T Achieva MRI using a 6-channel head coil, 1.5 Intera Scanner using 2 surface coils, Philips, Best, The Netherlands) and quantitative CBF values were calculated and compared between the different setups. Additionally, in eight patients with glioblastoma multiforme, ASL was used pre-, intra-, and postoperatively to define tumor tissue and the extent of resection in comparison to structural imaging. Results: A high correlation (r=0.91–0.96) was found between MRI scanners and coils used. ASL was as reliable as conventional MR imaging if complete resection was already achieved, but additionally provided valuable information regarding residual tumor tissue in one patient. Conclusions: Intraoperative arterial spin-labeling is a feasible, reproducible, and reliable tool to map CBF in brain tumors and seems to give beneficial information compared to conventional intraoperative MR imaging in partial resection. Keywords: Arterial spin labeling, ASL, Intraoperative, Monitoring, Perfusio

Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences

Impact of peritumoral brain edema on pre- and postoperative clinical conditions and on long-term outcomes in patients with intracranial meningiomas

Abstract Background Peritumoral brain edema (PTBE) is a common complication related to intracranial meningiomas. In several studies, researchers have investigated the pathogenesis of PTBE, and the factors involved in its development in patients with intracranial meningiomas have been reported. However, very little is known about the clinical effect of PTBE on patients with intracranial meningiomas; therefore, a systematic examination of this matter is necessary. Methods In this study, we performed a systematic examination of 696 patients with primary intracranial meningiomas to assess the effect of preoperative PTBE on preoperative symptoms, neurological deficits and postoperative complications, and long-term outcomes with a follow-up period of 16.8 years. We performed a univariate analysis and multiple regression for specific outcomes and adjusted for other relevant clinical factors. Results A total of 627 (90.1%) patients were symptomatic preoperatively. One hundred eighty-eight (90.8%) patients with small to moderate PTBE and 125 (98.4%) patients with severe PTBE presented with symptoms significantly more often than the 314 (86.7%) patients without PTBE (p < 0.001, univariate analysis). Cognitive deficits, palsy and seizure were significantly more present, preoperatively, in patients with PTBE than in patients without PTBE (p < 0.001, univariate analysis). Two hundred fifty-five (36.6%) patients experienced surgical and systemic complications postoperatively. The complication rate was significantly higher in patients with PTBE; 41.5% for patients with small to moderate PTBE and 52.8% for patients with severe PTBE, compared to 28.2% of patients without PTBE (p < 0.001, univariate analysis). Furthermore, pre- and postoperative KPS scores were significantly lower in patients with PTBE (p < 0.001). Patients with PTBE required additional medical support significantly more often (p < 0.001) and had a significantly longer hospital stay (p < 0.001). The mortality rate was higher in patients with PTBE immediately after surgery and in the follow-up period; however, the difference was not significant. The neurological condition of all patients improved in the follow-up and did not show significant differences between patients with and without preoperative PTBE (p = 0.6361). Multiple logistic regression analyses revealed a significant association between PTBE and the presence of preoperative cognitive deficits, the incidences of seizure and postoperative complications, and low pre- and postoperative KPS scores. Conclusions Preoperative PTBE significantly increased the incidences of specific preoperative symptoms, neurological deficits and postoperative complications in patients with intracranial meningiomas. After surgery, patients with preoperative PTBE required medical support significantly more often than patients without PTBE. However, all patients had favorable outcomes after surgery