The response of bispectral index to laryngoscopy, comparison between hemispheres in patients with a brain tumour versus a healthy control group

Background and Goal of Study: Electroencephalogram during anaesthesia may be affected by brain tumour.(1) We studied whether patients with a brain tumour have different BIS responses after laryngoscopy (LAR). We compared tumour patients with healthy control patients. Materials and Methods: After EC approval, 40 ASA 1 or 2 patients (control) and 41 intracranial tumour patients(tumour) received standardized anaesthesia while measuring bilateral BIS (BIS VISTAXP4 with bilateral sensor).(Covidien, Dublin, Ireland) Remifentanil was randomized to 3 or 5ng/ml effect‐site concentration (Minto) and maintained throughout the study. Propofol effect‐site concentration(CePROP)(Schnider) was set at 2 μg/ml and increased with incremental steps of 0.5 μg/ml until loss of consciousness was observed. After 3 minutes, laryngoscopy was performed and BIS was monitored during one minute. The median BIS of 1 minute before LAR is subtracted from the median BIS one minute after LAR to obtain delta BIS for each hemisphere. We tested if delta BIS is significantly different between hemispheres in control, between healthy and diseased hemispheres in tumour and between ipsilateral control and tumour hemispheres. Statistical significance was set at p< 0.05. Results and Discussion: No demographic differences were present except for age.(table 1) Delta BIS is not statistically different, neither between hemispheres in control, nor between healthy and diseased hemispheres in tumour groups.(table 2) No significant difference was found in delta BIS between ipsilateral control and pathological hemispheres. Conclusion(s): Bilateral BIS does not provide additional information on responsiveness to a standardized stimulus. We could not observe major differences in bilateral BIS response between control and brain tumour patients. Unilateral BIS monitoring seems to be equally informative in healthy and brain tumour patients compared to bilateral monitoring

Outcome of anterior lumbar interbody fusion : a retrospective study of clinical and radiologic parameters

Objective. This study aims to critically evaluate the long-term results of stand-alone anterior lumbar interbody fusion (ALIF), without use of rhBMP-2, as a therapeutic option for symptomatic patients with degenerative disc disease (DDD). Furthermore this study intends to identify predictive parameters for anterior lumbar interbody fusion outcome. Methods. A retrospective cohort study with additional telephone interview to obtain missing data was performed. All patients who underwent a L4-L5 and/or L5-S1 ALIF-procedure in the period between 2006 and 2011 were identified. The medical files of 123 patients with 154 fusion levels were reviewed. All patients were contacted by phone to gather supplementary and missing information. Pain and functionality scores (Visual Analogue Scale [VAS] and Oswestry Disability Index [ODI]), radiological (intervertebral disc height, Modic and Pfirrmann classifications) and different clinical parameters were gathered. Results. The mean age at surgery of the population was 46.2 years. Overall, 59 female and 64 male patients were included in the study. The mean visual analogue scales (VAS) for back and leg pain improved significantly (P<0.001) with 5 and 4.4 points respectively at 3 years follow-up. Modic-type I changes are associated with a better improvement in VAS-score for back pain (P=0.026), Pfirrmann-grades IV and V and an intervertebral disc height of less than 5 mm are associated with a better improvement in leg pain (respective P-values: 0.045 and 0.033). Overall, 89% of patients would reconsider the surgical intervention. Conclusions. The ALIF-technique is a durable treatment option for patients with DDD. This study suggests different predictive parameters for treatment outcome

Relation between telomerase activity, hTERT and telomere length for intracranial tumours

Human linear chromosomes are capped by specialized DNA-protein structures called telomeres. The present study analysed the telomerase activity, hTERT protein and telomere length in meningiomas and gliomas in relation to their WHO grading. Fifty-three freshly dissected tumour biopsies were analysed for telomerase activity, hTERT protein expression and telomere length. Telomerase activity was examined in 41 of the 53 biopsies. Telomerase activity was detected in 3 of 35 (8.6%) screened meningiomas (I benign, 1 atypical and I malignant meningioma). For hTERT expression, 56.4% of meningiomas were positive with a mean labelling index (hTERT LI) of 31.3% (SD=26.5) for the hTERT positive meningiomas. The mean telomere length for meningiomas was 6.983 kb (SD=1.969). For gliomas, no active telomerase was detected in 2 low-grade astrocytomas, whereas three of the four screened glioblastomas were positive for telomerase activity. The only hTERT protein positive astrocytoma had a mean labelling index of 9.0%. On the other hand, the hTERT LI for glioblastomas was 53.6% (SD=28.0). The two low-grade astrocytomas had a telomere length of 14.310 and 9.236 kb. The anaplastic astrocytoma had a telomere length of 4.903 kb and the glioblastomas 5.767 kb (SD=2.042). The normal meningeal and neuronal tissue is negative for telomerase activity and hTERT. The length was +/- 10.000 kb. These results indicate that telomere shortening may be a critical step in pathogenesis of atypical and malignant meningiomas and gliomas. Critical telomere shortening in vitro was shown to activate telomerase

Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma : a preclinical F98 glioblastoma rat model study

Purpose Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model. Procedures Female Fischer rats were inoculated with +/- 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model. Results Significant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group. Conclusion Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy

Kinetic modeling and graphical analysis of 18F-fluoromethylcholine (FCho), 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) PET for the discrimination between high-grade glioma and radiation necrosis in rats

Background : Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results. Methods : Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed. Results : The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k(3)) in GB (0.07 min(-1)) compared to RN (0.04 min(-1)) (p = 0.017). K-1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN. Conclusions : Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN