Enabling Navigation and Augmented Reality in the Sitting Position in Posterior Fossa Surgery Using Intraoperative Ultrasound.

Despite its broad use in cranial and spinal surgery, navigation support and microscope-based augmented reality (AR) have not yet found their way into posterior fossa surgery in the sitting position. While this position offers surgical benefits, navigation accuracy and thereof the use of navigation itself seems limited. Intraoperative ultrasound (iUS) can be applied at any time during surgery, delivering real-time images that can be used for accuracy verification and navigation updates. Within this study, its applicability in the sitting position was assessed. Data from 15 patients with lesions within the posterior fossa who underwent magnetic resonance imaging (MRI)-based navigation-supported surgery in the sitting position were retrospectively analyzed using the standard reference array and new rigid image-based MRI-iUS co-registration. The navigation accuracy was evaluated based on the spatial overlap of the outlined lesions and the distance between the corresponding landmarks in both data sets, respectively. Image-based co-registration significantly improved (p < 0.001) the spatial overlap of the outlined lesion (0.42 ± 0.30 vs. 0.65 ± 0.23) and significantly reduced (p < 0.001) the distance between the corresponding landmarks (8.69 ± 6.23 mm vs. 3.19 ± 2.73 mm), allowing for the sufficient use of navigation and AR support. Navigated iUS can therefore serve as an easy-to-use tool to enable navigation support for posterior fossa surgery in the sitting position.

Defining the role of surgery for patients with multiple brain metastases.

PURPOSE: To better define the role of surgery, we investigated survival and functional outcomes in patients with multiple brain metastases. METHODS: Pertinent clinical and radiological data of 131 consecutive patients (156 surgeries) were analyzed retrospectively. RESULTS: Surgical indications included mass effect (84.6%) and need for tissue acquisition (44.9%, for molecularly informed treatment: 10 patients). Major (i.e. CTCAE grade 3-5) neurological, surgical and medical complication were observed in 6 (3.8%), 12 (7.7%), and 12 (7.7%) surgical cases. Median preoperative and discharge KPS were 80% (IQF: 60-90%). Median overall survival (mOS) was 7.4 months. However, estimated 1 and 2 year overall survival rates were 35.6% and 25.1%, respectively. Survival was dismal (i.e. mOS ≤ 2.5 months) in patients who had no postoperative radio- and systemic therapy, or who incurred major complications. Multivariate analysis with all parameters significantly correlated with survival as univariate parameters revealed female sex, oligometastases, no major new/worsened neurological deficits, and postoperative radio- and systemic therapy as independent positive prognostic parameters. Univariate positive prognostic parameters also included histology (best survival in breast cancer patients) and less than median (0.28 cm3) residual tumor load. CONCLUSIONS: Surgery is a reasonable therapeutic option in many patients with multiple brain metastases. Operations should primarily aim at reducing mass effect thereby preserving the patients' functional health status which will allow for further local (radiation) and systemic therapy. Surgery for the acquisition of metastatic tissue (more recently for molecularly informed treatment) is another important surgical indication. Cytoreductive surgery may also carry a survival benefit by itself.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

The role of cytoreductive surgery in multifocal/multicentric glioblastomas.

PURPOSE: Multifocal/multicentric glioblastomas (mGBM) account for up to 20% of all newly diagnosed glioblastomas. The present study investigates the impact of cytoreductive surgery on survival and functional outcomes in patients with mGBM. METHODS: We retrospectively reviewed clinical and imaging data of 71 patients with newly diagnosed primary (IDH1 wildtype) mGBM who underwent operative treatment in 2015-2020 at the authors' institution. Multicentric/multifocal growth was defined by the presence of ≥ 2 contrast enhancing lesions ≥ 1 cm apart from each other. RESULTS: 36 (50.7%) patients had a resection and 35 (49.3%) a biopsy procedure. MGMT status, age, preoperative KPI and NANO scores as well as the postoperative KPI and NANO scores did not differ significantly between resected and biopsied cases. Median overall survival was 6.4 months and varied significantly with the extent of resection (complete resection of contrast enhancing tumor: 13.6, STR: 6.4, biopsy: 3.4 months; P = 0.043). 21 (58.3%) of resected vs. only 12 (34.3%) of biopsied cases had radiochemotherapy (p = 0.022). Multivariate analysis revealed chemo- and radiotherapy and also (albeit with smaller hazard ratios) extent of resection (resection vs. biopsy) and multicentric growth as independent predictors of patient survival. Involvement of eleoquent brain regions, as well as neurodeficit rates and functional outcomes did not vary significantly between the biopsy and the resection cohorts. CONCLUSION: Resective surgery in mGBM is associated with better survival. This benefit seems to relate prominently to an increased number of patients being able to tolerate effective adjuvant therapies after tumor resections. In addition, cytoreductive surgery may have a survival impact per se.

'Hippocampal innate inflammatory gliosis only' in pharmacoresistant temporal lobe epilepsy.

Drug-resistant mesial-temporal lobe epilepsy is a devastating disease with seizure onset in the hippocampal formation. A fraction of hippocampi samples from epilepsy-surgical procedures reveals a peculiar histological pattern referred to as 'gliosis only' with unresolved pathogenesis and enigmatic sequelae. Here, we hypothesize that 'gliosis only' represents a particular syndrome defined by distinct clinical and molecular characteristics. We curated an in-depth multiparameter integration of systematic clinical, neuropsychological as well as neuropathological analysis from a consecutive cohort of 627 patients, who underwent hippocampectomy for drug-resistant temporal lobe epilepsy. All patients underwent either classic anterior temporal lobectomy or selective amygdalohippocampectomy. On the basis of their neuropathological exam, patients with hippocampus sclerosis and 'gliosis only' were characterized and compared within the whole cohort and within a subset of matched pairs. Integrated transcriptional analysis was performed to address molecular differences between both groups. 'Gliosis only' revealed demographics, clinical and neuropsychological outcome fundamentally different from hippocampus sclerosis. 'Gliosis only' patients had a significantly later seizure onset (16.3 versus 12.2 years, P = 0.005) and worse neuropsychological outcome after surgery compared to patients with hippocampus sclerosis. Epilepsy was less amendable by surgery in 'gliosis only' patients, resulting in a significantly worse rate of seizure freedom after surgery in this subgroup (43% versus 68%, P = 0.0001, odds ratio = 2.8, confidence interval 1.7-4.7). This finding remained significant after multivariate and matched-pairs analysis. The 'gliosis only' group demonstrated pronounced astrogliosis and lack of significant neuronal degeneration in contrast to characteristic segmental neuron loss and fibrillary astrogliosis in hippocampus sclerosis. RNA-sequencing of gliosis only patients deciphered a distinct transcriptional programme that resembles an innate inflammatory response of reactive astrocytes. Our data indicate a new temporal lobe epilepsy syndrome for which we suggest the term 'Innate inflammatory gliosis only'. 'Innate inflammatory gliosis only' is characterized by a diffuse gliosis pattern lacking restricted hippocampal focality and is poorly controllable by surgery. Thus, 'innate inflammatory gliosis only' patients need to be clearly identified by presurgical examination paradigms of pharmacoresistant temporal lobe epilepsy patients; surgical treatment of this subgroup should be considered with great precaution. 'Innate inflammatory gliosis only' requires innovative pharmacotreatment strategies.

Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS).

Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20-50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10-8-7.5 × 10-3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.

Preoperative and postoperative memory in epilepsy patients with 'gliosis only' versus hippocampal sclerosis: a matched case-control study.

BACKGROUND: Gliosis only (GO) and hippocampal sclerosis (HS) are distinct histopathological entities in mesial temporal lobe epilepsy. This study explores whether this distinction also exists on a functional level when evaluating pre- and postoperative memory. METHODS: Using a retrospective matched case-control study design, we analysed verbal and visual memory performance in 49 patients with GO and 49 patients with HS before and one year after elective surgery. RESULTS: Clinical differences were evident with a later age at seizure onset (18±12 vs 12±9 years) and fewer postoperative seizure-free patients in the GO group (63% vs 82%). Preoperatively, group and individual-level data demonstrated that memory impairments were less frequent, less severe and relatively non-specific in patients with GO compared with HS. Postoperatively, verbal memory declined in both groups, particularly after left-sided resections, with more significant losses in patients with GO. Factoring in floor effects, GO was also associated with more significant visual memory loss, particularly after left resections. CONCLUSIONS: Compared with HS, GO is characterised by (1) a later onset of epilepsy, (2) less pronounced and more non-specific memory impairments before surgery, (3) a less successful surgical outcome and (4) a more significant memory decline after surgery. Overall, our results regarding cognition provide further evidence that GO and HS are distinct clinical entities. Functional integrity of the hippocampus appears higher in GO, as indicated by a better preoperative memory performance and worse memory outcome after surgery. The different risk-benefit ratios should be considered during presurgical patient counselling.

Clinical and Computerized Volumetric Analysis of Posterior Fossa Decompression for Space-Occupying Cerebellar Infarction.

Background and Purpose: Surgical decompression of the posterior fossa is often performed in cases with a space-occupying cerebellar infarction to prevent coma and death. In this study, we analyzed our institutional experience with this condition. We specifically attempted to address timing issues and investigated the role of cerebellar necrosectomy using imaging data and conducting volumetric analyses. Methods: We retrospectively studied pertinent clinical and imaging data, including computerized volumetric analyses (preoperative/postoperative infarction volume, necrosectomy volume, and posterior fossa volume), from all 49 patients who underwent posterior fossa decompression surgery for cerebellar infarction in our department from January 2012 to January 2021. Results: Thirty-five (71%) patients had a Glasgow Coma Scale (GCS) of 14-15 at admission vs. only 14 (29%) before vs. 41 (84%) following surgery. Seven (14%) patients had preventive surgery (initial GCS 14-15, preoperative GCS change ≤ 1). Only 18 (37%) patients had an mRS score of 0-3 at discharge. Estimated overall survival was 70.5% at 1 year. Interestingly, 18/20 (90%) surviving cases had a modified Rankin Scale (mRS) outcome of 0-3 (mRS 0-2: 12/20 [60%]) 1 year after surgery. Surgical timing, including preventive surgery and mass effect of the infarct, in the posterior fossa assessed semi-quantitatively (Kirollos grade) and with volumetric parameters that were not predictive of the patients' (functional) outcomes. Conclusion: Posterior fossa decompression for cerebellar infarction is a life-saving procedure, but rapid recovery of the GCS after surgery does not necessarily translate into good functional outcome. Many patients died during follow-up, but long-term mRS outcomes of 4-5 are rare. Surgery should probably aim primarily at pressure relief, and our clinical as well as volumetric data suggest that the impact of removing an infarcted tissue may be limited. It is presumably relatively safe to initially withhold surgery in cases with a GCS of 14-15.

The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts.

INTRODUCTION: Tumor Treating Fields (TTFields, 200 kHz) therapy is a noninvasive, locoregional cancer treatment approved for use in newly diagnosed glioblastoma (GBM), recurrent GBM, and malignant pleural mesothelioma. GBM patients with hydrocephalus may require implantation of a ventriculoperitoneal (VP) shunt, however, the current TTFields therapy label does not include the use of VP shunts in GBM patients due to insufficient safety data. This analysis evaluates the safety of TTFields therapy use in this population. METHODS: Unsolicited post-marketing global surveillance data from patients with GBM and a VP shunt (programmable/non-programmable) who received TTFields therapy between November 2012-April 2021 were retrospectively analyzed. Adverse events (AEs) were assessed using the Medical Dictionary for Regulatory Activities version 24.0. RESULTS: Overall, 156 patients with VP shunts were identified and included in this analysis. In total, 77% reported ≥ 1 AE; the most common TTFields therapy-related AEs were non-serious and localized, beneath-array skin AEs (43%). The incidence and categories of AEs were comparable between patients with or without VP shunts. Six patients with VP shunts experienced seven serious TTFields therapy-related AEs: skin erosion at the shunt site (n = 3); wound dehiscence at the shunt site (n = 2) and at the resection scar (n = 2). No shunt malfunctions were deemed related to TTFields therapy. CONCLUSIONS: In the real-world setting, TTFields therapy in GBM patients with VP shunts demonstrated good tolerability and a favorable safety profile. There was no evidence that TTFields therapy disrupted VP shunt effectiveness. These results suggest TTFields therapy may be safely used in patients with VP shunts.

Surgical Treatment of Cerebellar Metastases: Survival Benefits, Complications and Timing Issues.

We retrospectively studied 73 consecutive patients who underwent surgery 2015-2020 for removal of cerebellar metastases (CM). Median overall survival (medOS) varied widely between patients and compared favorably with the more recent literature (9.2, 25-75% IQR: 3.2-21.7 months vs. 5-8 months). Prognostic factors included clinical (but not radiological) hydrocephalus (medOS 11.3 vs. 5.2 months, p = 0.0374). Of note, a third of the patients with a KPI <70% or multiple metastases survived >12 months. Chemotherapy played a prominent prognostic role (medOS 15.5 vs. 2.3, p < 0.0001) possibly reflecting advances in treating systemic vis-à-vis controlled CNS disease. Major neurological (≥30 days), surgical and medical complications (CTCAE III-V) were observed in 8.2%, 13.7%, and 9.6%, respectively. The occurrence of a major complication markedly reduced survival (10.7 vs. 2.5 months, p = 0.020). The presence of extracerebral metastases did not significantly influence OS. Postponing staging was not associated with more complications or shorter survival. Together these data argue for individualized decision making which includes offering surgery in selected cases with a presumably adverse prognosis and also occasional urgent operations in cases without a preoperative oncological work-up. Complication avoidance is of utmost importance.

Unequal Impact of COVID-19 on Private and Academic Neurosurgical Workforce: Results of an International Survey.

Background: Since the COVID-19 outbreak several manuscripts regarding neurosurgical practice during this pandemic have been published. Qualitative studies on how the pandemic affected neurosurgeons, with additional focus on their practice, are still scarce. This study's objective was to investigate the impact of COVID-19 on various aspects of the professional and private life of a homogeneous group of international neurosurgeons affiliated to the European Association of Neurosurgical Societies (EANS). Methods: Neurosurgeons from Europe and abroad were invited to participate in an online survey endorsed by the Individual Membership Committee of the EANS. The survey captured a subjective snapshot of the impact of the first wave of the COVID-19 pandemic on EANS members and was advertised through its Institutional website. In addition to departmental data, personal feeling of safety, financial security, local precautions, number of surgeries performed, changes in daily routine, and other practice-related information were inquired. Differences among practice types were closely reviewed. Results: The survey was distributed between April and May 2020: 204 neurosurgeons participated. Participants were typically active EANS members (73%), consultants (57.9%), from university hospitals (64.5%). Elective surgical practice was still ongoing only for 15% of responders, whereas 18.7% of them had already transitioned to COVID-19 and emergency medical services. While 65.7% of participants thought their institutions were adequately prepared, lack of testing for SARS-CoV-2, and scarcity of personal protective equipment were still a matter of concern for most of them. Overall surgical activity dropped by 68% (cranial by 54%, spine by 71%), and even emergencies decreased by 35%. COVID-19 prompted changes in communication in 74% of departments, 44% increased telemedicine by >50%. While most neurosurgeons had concerns about personal and families' health, financial outlook appeared to be gloomy only for private practitioners. Conclusion: The lockdown imposed in many countries by the COVID-19 outbreak called for immediate modification of working routine and resulted in a dramatic decrease of elective surgical procedures. Neurosurgeons share common concerns but were not equally exposed to the personal health and financial dangers of the ongoing pandemic.

Collective-Mode Enhanced Matter-Wave Optics.

In contrast to light, matter-wave optics of quantum gases deals with interactions even in free space and for ensembles comprising millions of atoms. We exploit these interactions in a quantum degenerate gas as an adjustable lens for coherent atom optics. By combining an interaction-driven quadrupole-mode excitation of a Bose-Einstein condensate (BEC) with a magnetic lens, we form a time-domain matter-wave lens system. The focus is tuned by the strength of the lensing potential and the oscillatory phase of the quadrupole mode. By placing the focus at infinity, we lower the total internal kinetic energy of a BEC comprising 101(37) thousand atoms in three dimensions to 3/2 k_{B}·38_{-7}^{+6} pK. Our method paves the way for free-fall experiments lasting ten or more seconds as envisioned for tests of fundamental physics and high-precision BEC interferometry, as well as opens up a new kinetic energy regime.

Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review.

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine. Neuroinflammation in general, and IL-6 signaling in particular, appear to play a major role in the pathobiology and pathophysiology of aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Most importantly, elevated IL-6 CSF (rather than serum) levels appear to correlate with delayed cerebral ischemia (DCI, "vasospasm") and secondary ("vasospastic") infarctions. IL-6 CSF levels may also reflect other forms of injury to the brain following SAH, i.e., early brain damage and septic complications of SAH and aneurysm treatment. This would explain why many researchers have found an association between IL-6 levels and patient outcomes. These findings clearly suggest CSF IL-6 as a candidate biomarker in SAH patients. However, at this point, discrepant findings in variable study settings, as well as timing and other issues, e.g., defining proper clinical endpoints (i.e., secondary clinical deterioration vs. angiographic vasospasm vs. secondary vasospastic infarct) do not allow for its routine use. It is also tempting to speculate about potential therapeutic measures targeting elevated IL-6 CSF levels and neuroinflammation in SAH patients. Corticosteroids and anti-platelet drugs are indeed used in many SAH cases (not necessarily with the intention to interfere with detrimental inflammatory signaling), however, no convincing benefit has been demonstrated yet. The lack of a robust clinical perspective against the background of a relatively large body of data linking IL-6 and neuroinflammation with the pathophysiology of SAH is somewhat disappointing. One underlying reason might be that most relevant studies only report correlative data. The specific molecular pathways behind elevated IL-6 levels in SAH patients and their various interactions still remain to be delineated. We are optimistic that future research in this field will result in a better understanding of the role of neuroinflammation in the pathophysiology of SAH, which in turn, will translate into the identification of suitable biomarkers and even potential therapeutic targets.

Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage.

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4-14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4-14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4-14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

Quality of life in elderly patients after surgery for drug-resistant epilepsy - The impact of seizure outcome, neurological deficits and anxiety.

INTRODUCTION: Health related quality of life (HRQoL) has become a pivotal outcome parameter after surgery for drug-resistant epilepsy. The aim of the study was to investigate HRQoL and its relationship to seizure outcome, neurological deficits and anxiety after epilepsy surgery in a specific subpopulation of elderly patients. METHODS: A total of 85 elderly patients (older than 50 years) answered a standardized HRQoL questionnaire one year after epilepsy surgery. The questionnaire addressed the present self-assessed HRQoL in four subdomains (physical function, cognitive function, mood, social interaction). The questionnaire was based on the "Epilepsy Surgery Inventory-55", adapted for use in German speaking patients and validated by the QOLIE -10 and Beck Depression Inventory. RESULTS: A total of 51 patients (60%) were completely seizure free (ILAE1) at last available outcome (LAO). Permanent neurological deficits were observed in 8 patients (7%). Correlation analysis confirmed significant association between seizure outcome and overall HRQoL (r = -0.368, p < .001). New permanent neurological deficits showed impact on both HRQoL and the "cognitive function" subdomain. Anxiety and subjective assessment of postoperative status were strongly correlated with overall HRQoL (r = 0.692, p < .001 and r = 0.591, p < .001 respectively) and remained as independent prognostic factors in a multivariate regression analysis. CONCLUSION: Surgery for drug-resistant epilepsy in elderly improves patients' HRQoL. Both seizure freedom and new neurological deficits influence overall HRQoL. Interestingly, anxiety and patients' subjective assessment of postoperative status showed the highest impact on HRQoL in this subpopulation of epilepsy patients.

Early postoperative seizures (EPS) in patients undergoing brain tumour surgery.

Early postoperative seizures (EPS) are a common complication of brain tumour surgery. This paper investigates risk factors, management and clinical relevance of EPS. We retrospectively analysed the occurrence of EPS, clinical and laboratory parameters, imaging and histopathological findings in a cohort of 679 consecutive patients who underwent craniotomies for intracranial tumours between 2015 and 2017. EPS were observed in 34/679 cases (5.1%), with 14 suffering at least one generalized seizure. Patients with EPS had a worse postoperative Karnofsky performance index (KPI; with EPS, KPI < 70 vs. 70-100: 11/108, 10.2% vs. 23/571, 4.0%; p = 0.007). Preoperative seizure history was a predictor for EPS (none vs. 1 vs. ≥ 2 seizures: p = 0.037). Meningioma patients had the highest EPS incidence (10.1%, p < 0.001). Cranial imaging identified a plausible cause in most cases (78.8%). In 20.6%, EPS were associated with a persisting new neurological deficit that could not otherwise be explained. 34.6% of the EPS patients had recurrent seizures within one year. EPS require an emergency work-up. Multiple EPS and recurrent seizures are frequent, which indicates that EPS may also reflect a more chronic condition i.e. epilepsy. EPS are often associated with persisting neurological worsening.

Surgery for temporal lobe epilepsy in the elderly: Improving quality of life despite cognitive impairment.

INTRODUCTION: Temporal lobe epilepsy (TLE) surgery is still underutilized, especially in the elderly population because of concerns related to postoperative complication rate and cognitive deterioration. The aim of the study was to evaluate surgical data, quality of life and neuropsychological outcome in elderly patients, who underwent resective surgery for drug resistant TLE. METHODS AND MATERIALS: All patients underwent standardized presurgical assessment including clinical, neuroradiological, neuropsychological, and EEG examination. Elderly were considered all patients being 50 years or above (mean 56 yr., range 50-71 yr.). Neuropsychology was assessed before and after surgery, health-related quality of life (HRQOL) only after surgery. RESULTS: A total of 94 consecutive elderly patients were analyzed. Temporo-mesial resections were performed in 85 patients (90 %). Seizure outcome was available in all patients with a mean follow-up of 5.2 years (1.2-19 ± 3.75 years). 57 patients (60.6 %) were completely seizure free (ILAE 1). The overall morbidity was 10 % including 5 surgical complications and 5 permanent neurological deficits. Neuropsychological assessments in 60 patients showed considerable preoperative impairment, losses in different domains in 25-45 % and gains in about 25 % of the patients. Postoperative HRQOL data was available in 75 patients, revealing significant increase of HRQOL in all domains. Complete seizure freedom was the strongest predictor for postoperative HRQOL (p < 0.001). CONCLUSION: Surgery for drug resistant temporal lobe epilepsy is a feasible option for elderly patients as seizure control rates are comparable to the younger population. The acceptable rate of permanent neurological deficits and relevant improvements in quality of life, despite considerable postoperative cognitive impairment, justify surgical resection in properly selected elderly patients.

Age-, tumor-, and metastatic tissue-associated DNA hypermethylation of a T-box brain 1 locus in human kidney tissue.

BACKGROUND: While a considerable number of tumor-specific hypermethylated loci have been identified in renal cell cancer (RCC), DNA methylation of loci showing successive increases in normal, tumoral, and metastatic tissues could point to genes with high relevance both for the process of tumor development and progression. Here, we report that DNA methylation of a locus in a genomic region corresponding to the 3'UTR of the transcription factor T-box brain 1 (TBR1) mRNA accumulates in normal renal tissues with age and possibly increased body mass index. Moreover, a further tissue-specific increase of methylation was observed for tumor and metastatic tissue samples. RESULTS: Biometric analyses of the TCGA KIRC methylation data revealed candidate loci for age-dependent and tumor-specific DNA methylation within the last exon and in a genomic region corresponding to the 3'UTR TBR1 mRNA. To evaluate whether methylation of TBR1 shows association with RCC carcinogenesis, we measured 15 tumor cell lines and 907 renal tissue samples including 355 normal tissues, 175 tissue pairs of normal tumor adjacent and corresponding tumor tissue as well 202 metastatic tissues samples of lung, bone, and brain metastases by the use of pyrosequencing. Statistical evaluation demonstrated age-dependent methylation in normal tissue (R = 0.72, p < 2 × 10-16), association with adiposity (P = 0.019) and tumor-specific hypermethylation (P = 6.1 × 10-19) for RCC tissues. Comparison of tumor and metastatic tissues revealed higher methylation in renal cancer metastases (P = 2.65 × 10-6). CONCLUSIONS: Our analyses provide statistical evidence of association between methylation of TBR1 and RCC development and disease progression.