Which parameters influence cognitive, psychiatric and long-term seizure outcome in mesial temporal lobe epilepsy after selective amygdalohippocampectomy?

BACKGROUND: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. METHODS: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. RESULTS: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = - 2.341, p = 0.019). CONCLUSIONS: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

Feasibility, Clinical Potential, and Limitations of Trans-Burr Hole Ultrasound for Postoperative Evaluation of Chronic Subdural Hematoma: A Prospective Pilot Study.

BACKGROUND AND OBJECTIVES: Chronic subdural hematoma (CSDH) is commonly managed through burr hole surgery. Routine follow-up using computed tomography (CT) imaging is frequently used at many institutions, contributing to significant radiation exposure. This study evaluates the feasibility, safety, and reliability of trans-burr hole sonography as an alternative postoperative imaging modality, aiming to reduce radiation exposure by decreasing the frequency of CT scans. METHODS: We conducted a prospective pilot study on 20 patients who underwent burr hole surgery for CSDH. Postoperative imaging included both CT and sonographic examinations through the burr hole. We assessed the ability to measure residual subdural fluid thickness under the burr hole sonographically compared with CT, the occurrence of complications, and the potential factors affecting sonographic image quality. The Pearson correlation coefficient was used to demonstrate relationships between CT and ultrasound and axial and coronal ultrasound. RESULTS: Sonography through the burr hole was feasible in 73.5% of cases, providing measurements of residual fluid that closely paralleled CT findings, with an average discrepancy of 1.2 mm for axial and 1.4 mm for coronal sonographic views. A strong positive correlation was found between axial and coronal ultrasound (r = 0.955), CT and axial ultrasound (r = 0.936), and CT and coronal ultrasound (r = 0.920). The primary obstacle for sonographic imaging was the presence of air within the burr hole or the subdural space, which typically resolved over time after surgery. CONCLUSION: Trans-burr hole sonography emerges as a promising technique for postoperative monitoring of CSDH, with the potential to safely reduce reliance on CT scans and associated radiation exposure in selected patients. Our results support further investigation into the extended use of sonography during the follow-up phase. Prospective multicenter studies are recommended to establish the method's efficacy and to explore strategies for minimizing air presence postsurgery.

From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

OBJECTIVE: Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. METHODS: Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. RESULTS: A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. CONCLUSIONS: The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Machine learning based outcome prediction of microsurgically treated unruptured intracranial aneurysms.

Machine learning (ML) has revolutionized data processing in recent years. This study presents the results of the first prediction models based on a long-term monocentric data registry of patients with microsurgically treated unruptured intracranial aneurysms (UIAs) using a temporal train-test split. Temporal train-test splits allow to simulate prospective validation, and therefore provide more accurate estimations of a model's predictive quality when applied to future patients. ML models for the prediction of the Glasgow outcome scale, modified Rankin Scale (mRS), and new transient or permanent neurological deficits (output variables) were created from all UIA patients that underwent microsurgery at the Kepler University Hospital Linz (Austria) between 2002 and 2020 (n = 466), based on 18 patient- and 10 aneurysm-specific preoperative parameters (input variables). Train-test splitting was performed with a temporal split for outcome prediction in microsurgical therapy of UIA. Moreover, an external validation was conducted on an independent external data set (n = 256) of the Department of Neurosurgery, University Medical Centre Hamburg-Eppendorf. In total, 722 aneurysms were included in this study. A postoperative mRS > 2 was best predicted by a quadratic discriminant analysis (QDA) estimator in the internal test set, with an area under the receiver operating characteristic curve (ROC-AUC) of 0.87 ± 0.03 and a sensitivity and specificity of 0.83 ± 0.08 and 0.71 ± 0.07, respectively. A Multilayer Perceptron predicted the post- to preoperative mRS difference > 1 with a ROC-AUC of 0.70 ± 0.02 and a sensitivity and specificity of 0.74 ± 0.07 and 0.50 ± 0.04, respectively. The QDA was the best model for predicting a permanent new neurological deficit with a ROC-AUC of 0.71 ± 0.04 and a sensitivity and specificity of 0.65 ± 0.24 and 0.60 ± 0.12, respectively. Furthermore, these models performed significantly better than the classic logistic regression models (p < 0.0001). The present results showed good performance in predicting functional and clinical outcomes after microsurgical therapy of UIAs in the internal data set, especially for the main outcome parameters, mRS and permanent neurological deficit. The external validation showed poor discrimination with ROC-AUC values of 0.61, 0.53 and 0.58 respectively for predicting a postoperative mRS > 2, a pre- and postoperative difference in mRS > 1 point and a GOS < 5. Therefore, generalizability of the models could not be demonstrated in the external validation. A SHapley Additive exPlanations (SHAP) analysis revealed that this is due to the most important features being distributed quite differently in the internal and external data sets. The implementation of newly available data and the merging of larger databases to form more broad-based predictive models is imperative in the future.

A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use. Research question: The study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH. Material and methods: In this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment. Results: Ten patients across four dose groups were treated with NicaPlant® (3-13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm. Discussion and conclusion: The placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies.

Reduction of spondylolisthesis and restoration of lumbar lordosis after anterior lumbar interbody fusion (ALIF).

BACKGROUND: Anterior lumbar interbody fusion (ALIF) is a well-established surgical treatment option for various diseases of the lumbar spine, including spondylolisthesis. This study aimed to evaluate the postoperative correction of spondylolisthesis and restoration of lumbar and segmental lordosis after ALIF. METHODS: Patients with spondylolisthesis who underwent ALIF between 2013 and 2019 were retrospectively assessed. We assessed the following parameters pre-and postoperatively (6-months follow-up): Visual Analogue Scale (VAS) for pain, Oswestry Disability Index (ODI), lumbar lordosis (LL), segmental lordosis (SL), L4/S1 lordosis, and degree of spondylolisthesis. RESULTS: 96 patients were included. In 84 cases (87.50%), additional dorsal instrumentation was performed. The most frequent diagnosis was isthmic spondylolisthesis (73.96%). VAS was reduced postoperatively, from 70 to 40, as was ODI (50% to 32%). LL increased from 59.15° to 64.45°, as did SL (18.95° to 28.55°) and L4/S1 lordosis (37.90° to 44.00°). Preoperative spondylolisthesis was 8.90 mm and was reduced to 6.05 mm postoperatively. Relative spondylolisthesis was 21.63% preoperatively and 13.71% postoperatively. All clinical and radiological improvements were significant (all p < 0.001). No significant difference considering the lordosis values nor spondylolisthesis was found between patients who underwent ALIF surgery without dorsal instrumentation and patients who received additional dorsal instrumentation. Venous laceration was the most frequent complication (10.42%). CONCLUSIONS: With ALIF, good clinical results and safe and effective reduction of spondylolisthesis and restoration of lordosis can be achieved. Additional dorsal instrumentation does not significantly affect postoperative lordosis or spondylolisthesis. Individual vascular anatomy must be reviewed preoperatively before considering ALIF.

Surgeon experience in glioblastoma surgery of the elderly-a multicenter, retrospective cohort study.

PURPOSE: To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. METHODS: GBM patients aged ≥ 65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). RESULTS: 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0-12.0); median EOR was 89.4%. Surgery-related morbidity affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P < .001); patients with surgery-related morbidity were less likely to receive adjuvant treatment (P = .002). In multivariable testing, adjuvant therapy (P < .001; HR = 0.064, 95%CI 0.028-0.144) remained the only significant predictor for improved OS. CONCLUSION: Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial for generating a treatment benefit for this cohort.

Tailored Intraoperative MRI Strategies in High-Grade Glioma Surgery: A Machine Learning-Based Radiomics Model Highlights Selective Benefits.

BACKGROUND AND OBJECTIVES: In high-grade glioma (HGG) surgery, intraoperative MRI (iMRI) has traditionally been the gold standard for maximizing tumor resection and improving patient outcomes. However, recent Level 1 evidence juxtaposes the efficacy of iMRI and 5-aminolevulinic acid (5-ALA), questioning the continued justification of iMRI because of its associated costs and extended surgical duration. Nonetheless, drawing from our clinical observations, we postulated that a subset of intricate HGGs may continue to benefit from the adjunctive application of iMRI. METHODS: In a prospective study of 73 patients with HGG, 5-ALA was the primary technique for tumor delineation, complemented by iMRI to detect residual contrast-enhanced regions. Suboptimal 5-ALA efficacy was defined when (1) iMRI detected contrast-enhanced remnants despite 5-ALA's indication of a gross total resection or (2) surgeons observed residual fluorescence, contrary to iMRI findings. Radiomic features from preoperative MRIs were extracted using a U2-Net deep learning algorithm. Binary logistic regression was then used to predict compromised 5-ALA performance. RESULTS: Resections guided solely by 5-ALA achieved an average removal of 93.14% of contrast-enhancing tumors. This efficacy increased to 97% with iMRI integration, albeit not statistically significant. Notably, for tumors with suboptimal 5-ALA performance, iMRI's inclusion significantly improved resection outcomes (P-value: .00013). The developed deep learning-based model accurately pinpointed these scenarios, and when enriched with radiomic parameters, showcased high predictive accuracy, as indicated by a Nagelkerke R2 of 0.565 and a receiver operating characteristic of 0.901. CONCLUSION: Our machine learning-driven radiomics approach predicts scenarios where 5-ALA alone may be suboptimal in HGG surgery compared with its combined use with iMRI. Although 5-ALA typically yields favorable results, our analyses reveal that HGGs characterized by significant volume, complex morphology, and left-sided location compromise the effectiveness of resections relying exclusively on 5-ALA. For these intricate cases, we advocate for the continued relevance of iMRI.

Nonsteroidal anti-inflammatory drugs (NSAID) do not increase blood loss or the incidence of postoperative epidural hematomas when using minimally invasive fusion techniques in the degenerative lumbar spine.

Objective: Nonsteroidal anti-inflammatory drugs (NSAID) are essential in surgeons' armamentarium for pain relief and antiphlogistic effects. However, spine surgeons are concerned about the drugs' impact on coagulation, fearing hemodynamic instability due to blood loss and neurological complications due to postoperative hematoma. Furthermore, there are no clear guidelines for the use of these drugs. Materials and methods: In this retrospective subgroup analysis of a prospective observational study, we investigated 181 patients who underwent minimally invasive spinal fusions in degenerative lumbar spine pathologies. 83 patients were given NSAID perioperatively, 54 of which were female and 29 male. Of these patients who took NSAID, 39 were on NSAID until at least one day before surgery or perioperatively, whilst the others discontinued their NSAID medication at least three days before surgery. Differences in perioperative blood loss, as well as complication rates between patients with and without NSAID treatment, were investigated. Results: A significantly higher amount of blood loss during surgery and the monitoring period was encountered in patients whose spine was fused in more than one level, regardless of whether NSAID medication was taken or not and up until what point. Furthermore, it was found that taking NSAID medication had no effect on the incidence of postoperative epidural hematomas. Conclusion: Perioperatively taking NSAID medication does not increase blood loss or the incidence of postoperative hematoma in patients undergoing minimally invasive lumbar spinal fusion surgery.

Reconstruction of the cranial vault, surgical drainage of brain abscesses, and the treatment of rhinoliquorrhea: the "Luftwaffen Lazarett 6/XVII Bad Ischl," the first neurosurgical department in Austria.

The main purpose of neurosurgery during World War II was the treatment of traumatic brain injury, injuries to the spine, and injuries to peripheral nerves-mostly penetrating injuries caused by bullets or shrapnel. After heavy bombings of Berlin, in 1943 the main neurosurgical hospital was moved to Bad Ischl, a small town in the Austrian countryside. There, Wilhelm Toennis and his successor Dietrich W. Krueger made important observations treating soldiers suffering from traumatic brain injuries. During the war and also in the postwar period, they focused on techniques for the reconstruction of the cranial vault, the treatment of brain abscesses by drainage instead of extirpation, and also the treatment of rhinoliquorrhea due to frontobasal trauma. Their approaches were sometimes contradictory to the standard of care of the times. Nevertheless, many of the principles of the techniques described are still practiced by today's neurosurgeons.

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017-2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017-2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

Accidental Dural Tears in Minimally Invasive Spinal Surgery for Degenerative Lumbar Spine Disease.

Background: One of the most frequent complications of spinal surgery is accidental dural tears (ADTs). Minimal access surgical techniques (MAST) have been described as a promising approach to minimizing such complications. ADTs have been studied extensively in connection with open spinal surgery, but there is less literature on minimally invasive spinal surgery (MISS). Materials and Methods: We reviewed 187 patients who had undergone degenerative lumbar spinal surgery using minimally invasive spinal fusions techniques. We analyzed the influence of age, Body Mass Index (BMI), smoking, diabetes, and previous surgery on the rate of ADTs in MISS. Results: Twenty-two patients (11.764%) suffered from an ADT. We recommended bed rest for two and a half to 5 days, depending on the type of repair required and the amount of cerebrospinal fluid (CSF) leakage. We could not find any statistically significant correlation between ADTs and age (p = 0.34,), BMI (p = 0.92), smoking (p = 0.46), and diabetes (p = 0.71). ADTs were significantly more frequent in cases of previous surgery (p < 0.001). None of the patients developed a transcutaneous CSF leak or post-operative infection. Conclusions: The frequency of ADTs in MISS appears comparable to that encountered when using open surgical techniques. Additionally, MAST produces less dead space along the corridor to the spine. Such reduced dead space may not be enough for pseudomeningocele to occur, cerebrospinal fluid to accumulate, and fistula to form. MAST, therefore, provides a certain amount of protection.

Cortical and Subcortical Anatomy of the Orbitofrontal Cortex: A White Matter Microfiberdissection Study and Case Series.

BACKGROUND: The literature on white matter anatomy underlying the human orbitofrontal cortex (OFC) is scarce in spite of its relevance for glioma surgery. OBJECTIVE: To describe the anatomy of the OFC and of the underlying white matter fiber anatomy, with a particular focus on the surgical structures relevant for a safe and efficient orbitofrontal glioma resection. Based on anatomical and radiological data, the secondary objective was to describe the growth pattern of OFC gliomas. METHODS: The study was performed on 10 brain specimens prepared according to Klingler's protocol and dissected using the fiber microdissection technique modified according to U.T., under the microscope at high magnification. RESULTS: A detailed stratigraphy of the OFC was performed, from the cortex up to the frontal horn of the lateral ventricle. The interposed neural structures are described together with relevant neighboring topographic areas and nuclei. Combining anatomical and radiological data, it appears that the anatomical boundaries delimiting and guiding the macroscopical growth of OFC gliomas are as follows: the corpus callosum superiorly, the external capsule laterally, the basal forebrain and lentiform nucleus posteriorly, and the gyrus rectus medially. Thus, OFC gliomas seem to grow ventriculopetally, avoiding the laterally located neocortex. CONCLUSION: The findings in our study supplement available anatomical knowledge of the OFC, providing reliable landmarks for a precise topographical diagnosis of OFC lesions and for perioperative orientation. The relationships between deep anatomic structures and glioma formations described in this study are relevant for surgery in this highly interconnected area.

The influence of smoking in minimally invasive spinal fusion surgery.

BACKGROUND: The impact of smoking on spinal surgery has been studied extensively, but few investigations have focused on minimally invasive surgery (MIS) of the spine and the difference between complication rates in smokers and non-smokers. We evaluated whether a history of at least one pack-year preoperatively could be used to predict adverse peri- and postoperative outcomes in patients undergoing minimally invasive fusion procedures of the lumbar spine. In a prospective study, we assessed the clinical effectiveness of MIS in an unselected population of 187 patients. METHODS: We evaluated perioperative and postoperative complication rates in MIS fusion techniques of the lumbar spine in smoking and non-smoking patients. MIS fusion was performed using interbody fusion procedures and/or posterolateral fusion alone. RESULTS: Smokers were significantly younger than non-smokers. We did not encounter infection at the site of surgery or severe wound healing disorder in smokers. We registered no difference between the smoking and non-smoking groups with regard to peri- or postoperative complication rate, blood loss, or length of stay in hospital. We found a significant influence of smoking (p = 0.049) on the overall perioperative complication rate. CONCLUSION: MIS fusion techniques seem to be a suitable tool for treating degenerative spinal disorders in smokers.

Risks and Benefits of Glioblastoma Resection in Older Adults: A Retrospective Austrian Multicenter Study.

OBJECTIVE: To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms. METHODS: We retrospectively identified patients with GBM ≥65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors. RESULTS: The study population included 160 patients (mean age, 73.1 ± 5.1 years), and the median contrast-enhancing tumor volume was 31.0 cm3. Biomarker analyses revealed O(6)-methylguanine-DNA methyltransferase-promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5.4 months (95% confidence interval [CI], 4.6-6.4 months) and 10.0 months (95% CI, 7.9-11.7 months). The strongest predictors for favorable outcome were patient age ≤73.0 years (P = 0.0083), preoperative Karnofsky Performance Status Scale score ≥80% (P = 0.0179), postoperative modified Rankin Scale score ≤1 (P < 0.0001), adjuvant treatment (P < 0.0001), and no treatment-associated morbidity (P = 0.0478). Increased EOR did not correlate with survival (P = 0.5046), but correlated significantly with treatment-associated morbidity (P = 0.0031). CONCLUSIONS: Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.

The impact of type 2 diabetes on the peri- and postoperative outcomes of minimally invasive fusion techniques in the lumbar spine.

BACKGROUND: The impact of diabetes on spinal surgery has been studied extensively, but very few studies have focused on minimal access spinal technologies (MAST) and complication rates in patients suffering from type 2 diabetes (T2DM). Diabetes increases the risk of wound healing disorders, complication rate and length of stay in the hospital. We focused on the peri- and postoperative complications of MAST in an unselected consecutive population of 187 patients suffering from degenerative disorders lumbar spine disorders. Since mostly older patients are affected by degenerative lumbar changes, we concentrated on T2DM. METHODS: We evaluated perioperative and postoperative complication rates associated with MAST fusion techniques in lumbar spine surgery in patients suffering from T2DM compared to patients without diabetes. Lumbar fusion was performed using interbody and posterolateral fusion. RESULTS: Eighteen female and sixteen male patients suffered from T2DM (15.65% and 22.22% respectively). No differences between patients with and without T2DM concerning surgery-related complications including infections, severe wound healing disorders or length of in-hospital stay were noted. Peri- or postoperative complication rates, as well as blood loss volumes, were evenly distributed between the two groups. CONCLUSIONS: T2DM is not a risk factor for the occurrence of complications in MAST.

Assessment of brain delivery of a model ABCB1/ABCG2 substrate in patients with non-contrast-enhancing brain tumors with positron emission tomography.

BACKGROUND: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters expressed at the blood-brain barrier which effectively restrict the brain distribution of the majority of currently known anticancer drugs. High-grade brain tumors often possess a disrupted blood-brain tumor barrier (BBTB) leading to enhanced accumulation of magnetic resonance imaging contrast agents, and possibly anticancer drugs, as compared to normal brain. In contrast to high-grade brain tumors, considerably less information is available with respect to BBTB integrity in lower grade brain tumors. MATERIALS AND METHODS: We performed positron emission tomography imaging with the radiolabeled ABCB1 inhibitor [11C]tariquidar, a prototypical ABCB1/ABCG2 substrate, in seven patients with non-contrast -enhancing brain tumors (WHO grades I-III). In addition, ABCB1 and ABCG2 levels were determined in surgically resected tumor tissue of four patients using quantitative targeted absolute proteomics. RESULTS: Brain distribution of [11C]tariquidar was found to be very low across the whole brain and not significantly different between tumor and tumor-free brain tissue. Only one patient showed a small area of enhanced [11C]tariquidar uptake within the brain tumor. ABCG2/ABCB1 ratios in surgically resected tumor tissue (1.4 ± 0.2) were comparable to previously reported ABCG2/ABCB1 ratios in isolated human micro-vessels (1.3), which suggested that no overexpression of ABCB1 or ABCG2 occurred in the investigated tumors. CONCLUSIONS: Our data suggest that the investigated brain tumors had an intact BBTB, which is impermeable to anticancer drugs, which are dual ABCB1/ABCG2 substrates. Therefore, effective drugs for antitumor treatment should have high passive permeability and lack ABCB1/ABCG2 substrate affinity. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT), 2011-004189-13. Registered on 23 February 2012, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-004189-13.

Alterations in GABAA Receptor Subunit Expression in the Amygdala and Entorhinal Cortex in Human Temporal Lobe Epilepsy.

The amygdala has long been implicated in the pathophysiology of human temporal lobe epilepsy (TLE). The different nuclei of this complex structure are interconnected and share reciprocal connections with the hippocampus and other brain structures, partly via the entorhinal cortex. Expression of GABAA receptor subunits α1, α2, α3, α5, ß2, ß2/3, and γ2 was evaluated by immunohistochemistry in amygdala specimens and the entorhinal cortex of 12 TLE patients and 12 autopsy controls. A substantial decrease in the expression of α1, α2, α3, and ß2/3 subunits was found in TLE cases, accompanied by an increase of γ2 subunit expression in many nuclei. In the entorhinal cortex, the expression of all GABAA receptor subunits was decreased except for the α1 subunit, which was increased on cellular somata. The overall reduction in α subunit expression may lead to decreased sensitivity to GABA and its ligands and compromise phasic inhibition, whereas upregulation of the γ2 subunit might influence clustering and kinetics of receptors and impair tonic inhibition. The description of these alterations in the human amygdala is important for the understanding of network changes in TLE as well as the development of subunit-specific therapeutic agents for the treatment of this disease.

The influence of age on the peri- and postoperative clinical course in patients undergoing minimally invasive transforaminal lumbar interbody fusion techniques of the lumbar spine.

OBJECTIVE: As a result of continuously increasing life expectancy, the number of requests for surgery to treat degenerative diseases of the spine in the elderly population will increase. Since older age is associated with the occurrence of medical comorbidities, the demand for less extensive surgical approaches is growing. The aim of this study is to establish whether minimally invasive fusion techniques are a safe and adequate tool for use in elderly patients. PATIENTS AND METHODS: We analyzed 187 patients who underwent minimally invasive surgery (MIS) in the form of one- to four-level fusion procedures. In 146 patients, additional widening of the spinal canal was performed. The subjects were grouped into four age categories of approximately equal size (33-56, 56-66, 66-74 and 74-85). The effect of age on the incidence of peri- and postoperative complications was investigated and compared between the age groups. RESULTS: Older age was not associated with the occurrence of perioperative complications, which include wound healing disorders, hematomas, wound traction-blisters and cerebrospinal fluid leakage. Fourteen patients (7.49%) encountered distinct surgical technique related complications, making surgical revision necessary in eight patients (4.28%). Furthermore, increasing age didn't elevate the risk of postoperative adverse events, i.e. pulmonary embolism, ischemic heart attack or pneumonia, among others. However, older patients were found to stay in hospital longer than younger patients, especially when more than one level was fused. CONCLUSIONS: Minimally invasive surgery techniques are safe in elderly patients. The small-scale surgical approach guarantees a low incidence of infections and wound healing disorders. However, a longer hospital stay must be expected in older patients.

Surgical and Clinical Results of Minimally Invasive Spinal Fusion Surgery in an Unselected Patient Cohort of a Spinal Care Unit.

OBJECTIVES: To review the surgical results and to identify possible parameters influencing the clinical outcomes in an unselected patient collective undergoing minimally invasive lumbar interbody fusion in a spinal care unit. METHODS: A total of 229 adult patients who underwent minimally invasive lumbar spinal fusion between 2008 and 2016 were included in this retrospective analysis. Lumbar fusion was performed using transforaminal interbody fusion (TLIF) devices and posterolateral fusion. To eliminate confounding parameters, in all patients interbody fusion was indicated by lumbar degenerative pathologies, and surgery was performed using the same fusion device. Treatment efficacy was evaluated using scores describing pain (visual analogue scale [VAS]) and health impairment (EQ-5D, Oswestry Disability Index [ODI]). The influence of patient age, obesity, active smoking status, and co-morbidities on clinical outcome and perioperative complications was analyzed. RESULTS: The patient population reviewed had improved VAS (P(leg pain) ≤ 0.0001, P(back pain) ≤ 0.0001), ODI (P ≤ 0.0001), EQ-VAS (P ≤ 0.0001), and EQ-5D subscales "mobility", "self-care", "pain", and "anxiety" (P(mobility) ≤ 0.0001, P(self-care) = 0.41, P(pain) ≤ 0.0001, P(anxiety) = 0.011) postoperatively. Neither advanced patient age, nor increased body mass index (BMI), hypertension, or active smoking status had a significantly limiting influence on the success of minimally invasive spinal surgeries (MIS). Duration of surgery strongly correlated with the number of spinal levels treated and with intraoperative blood loss (r = 0.774, P ≤ 0.0001, n = 208). Weak positive correlations were found between patient age and duration of surgery (r = 0.184, P = 0.005, n = 229), intraoperative blood loss (r = 0.165, P = 0.012, n = 229), and duration of hospitalization (r = 0.270, P ≤ 0.0001, n = 228), respectively. When compared to non-smokers, smokers were younger (P ≤ 0.0001), and had a significantly lower BMI (P = 0.001), shorter durations of surgery (P ≤ 0.0001), decreased intraoperative blood loss (P = 0.022), and shorter hospital stays (P = 0.006), respectively. Complications occurred in 17 patients (7%) and were not affected by patient age, BMI, hypertension, or active smoking status. CONCLUSION: Minimally invasive spinal surgery is a safe and effective treatment option and may be superior to open surgery in subpopulations with significant co-morbidities and risk factors, such as elderly and obese patients as well as patients with an active smoking status.