Search

Methanol extracts of seven edible fruits found in southern Brazil: Garcinia achachairu, Rubus imperialis, Rubus rosaefolius, Solanum quitoense, Solanum sessiliflorun, Diospyros inconstans and Plinia glomerata, were evaluated for their total phenol content and antioxidant activity in different in vitro free radical scavenging models. In addition, studies were performed on cell viability of extracts of the seeds of G. achachairu against murine melanoma cells. The fruits peel and seeds of G. achachairu were very promising in terms of total phenol content (data in gallic acid equivalent per gram), as assessed by the Folin-Ciocalteu method, with values of 9.70±3.2 and 8.40±1.1, respectively. On the other hand, antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl scavenging assay showed that the fruit pulp and peel of P. glomerata presented the best profile, with values of the 16.3±1.8 and 15.9±2.4 μg/ml, respectively. Regarding the cytotoxic effect of methanol extract and guttiferone A from G. achachairu, we have observed that both inhibit the growth of B16F10 tumor cells, with calculated IC50 values of 49.6±2.1 mg/ml and 48.6±5.4 mM, respectively. [ABSTRACT FROM AUTHOR]

Study aim: this study examined the item difficulty and item discrimination scores for the HRFK PE Metrics cognitive assessment tool for 5th-grade students.

Background: Spontaneous intracerebral abscess formation is a rare condition presenting with a disabling sequela. The origin of infection can either be primary or secondary to an infection at another location. The site of primary infection - due to the proximity, often the oral cavity, the sinuses, and the orbit - determines the causative pathogens. Treatment often combines surgical and antimicrobial therapies. To determine the microbiology and respective changes and treatment outcome, we performed this retrospective monocentric cohort study of patients requiring surgical treatment of brain abscesses., Methods: Patients undergoing surgical treatment of a primary intracranial abscess between January 2000 and January 2021 in the Department of Neurosurgery, Freiburg University Hospital were included. Demographic, clinical and imaging data were extracted from patients' medical records and databases. Treatment approaches were also analyzed, and surgical therapy and antibiotic therapy were reported. Outcome was assessed by the modified Rankin score (mRS) and was dichotomized into good (mRS 0-3) and poor (mRS 4-6) outcome., Results: We included 65 patients with spontaneous intracerebral abscess that were treated with neurosurgical intervention at our institution. Analysis of the causative pathogens showed an increasing dominance of rare pathogens such as fungi, parasites, mycobacteria and anaerobes. Outcome measured by the mRS was similar from 2005 to 2021., Conclusions: The pathogen spectrum of spontaneous intracerebral abscess at our institution is shifting with rarer pathogens being increasingly detected. This retrospective analysis highlights the need for microbiological diagnosis and of combined surgical and antibiological treatment., Competing Interests: Declarations Disclosures None. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Recently, there is increasing evidence that the proportion of odontogenic brain abscesses is greater than previously known. In this study, we aim to differentiate the oral infections as triggers more precisely and to classify them in the clinical setting., Methods: For analysis, we conducted a retrospective single center study. We reviewed patients with brain abscesses who have undergone treatment in the University Hospital of Freiburg, Germany in the period between 2000-2021. Inclusion required two main criteria: 1. The brain abscess must not have an other focus than odontogenic. 2. The microbial spectrum identified in the brain abscess must be consistent with an odontogenic origin., Results: Of 217 brain abscess patients, 26 met the inclusion criteria. 42% (11 patients) suffered from immunosuppressive conditions. Odontogenic foci were diagnosed in 18 cases (69%). Neurologic deficits included vigilance reduction and hemiparesis. Pathogens of the Streptococcus anginosus group were the most frequent causative agent (21 cases, 81%). Metronidazole (54%) and ceftriaxone (42%) were part of the targeted antibiotic therapy. All brain abscesses were surgically treated. Teeth were extracted in 14 of 17 cases for focus control. 18 cases (72%) showed complete or partial resolution of neurologic symptoms and 3 cases were fatal., Conclusion: Apparently silent or chronic oral infections are sufficient to cause bacterial colonization of the brain, especially in immunocompromised patients. Therefore, special care should be taken to maintain good oral health. An interdisciplinary management should become a standard to prevent and treat the occurrence of brain abscesses., (© 2024. The Author(s).)

Background and Purpose: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of symptoms, most common being orthostatic headache. In addition, ventral spinal CSF leaks are a possible etiology of superficial siderosis (SS), a rare condition characterized by hemosiderin deposits in the central nervous system (CNS). The classical presentation of SS involves ataxia, bilateral hearing loss, and myelopathy. Unfortunately, treatment options are scarce. This study was undertaken to evaluate whether microsurgical closure of CSF leaks can prevent further clinical deterioration or improve symptoms of SS., Methods: This cohort study was conducted using data from a prospectively maintained database in two large spontaneous intracranial hypotension (SIH) referral centers in Germany and Switzerland of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. Patients with spinal CSF leaks were screened for the presence of idiopathic infratentorial symmetric SS of the CNS., Results: Twelve patients were included. The median latency between the onset of orthostatic headaches and symptoms attributed to SS was 9.5 years. After surgical closure of the underlying spinal CSF leak, symptoms attributed to SS improved in seven patients and remained stable in three. Patients who presented within 1 year after the onset of SS symptoms improved, but those who presented in 8-12 years did not improve. We could show a significant association between patients with spinal longitudinal extrathecal collections and SS., Conclusions: Long-standing untreated ventral spinal CSF leaks can lead to SS of the CNS, and microsurgical sealing of spinal CSF leaks might stop progression and improve symptoms in patients with SS in a time-dependent manner., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase ( MGMT )-methylated GBM cases. However, approximately 20% of patients with MGMT -unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients' clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.

Glioblastoma multiforme (GBM) remains one of the tumors with the worst prognosis. In recent years, a better overall survival (OS) has been described in cases subjected to Gross Total Resection (GTR) that were presenting hypermethylation of Methylguanine-DNA methyltransferase (MGMT) promoter. Recently, also the expression of specific miRNAs involved in MGMT silencing has been related to survival. In this study, we evaluate MGMT expression by immunohistochemistry (IHC), MGMT promoter methylation and miRNA expression in 112 GBMs and correlate the data to patients' clinical outcomes. Statistical analyses demonstrate a significant association between positive MGMT IHC and the expression of miR-181c, miR-195, miR-648 and miR-767.3p between unmethylated cases and the low expression of miR-181d and miR-648 and between methylated cases and the low expression of miR-196b. Addressing the concerns of clinical associations, a better OS has been described in presence of negative MGMT IHC, in methylated patients and in the cases with miR-21, miR-196b overexpression or miR-767.3 downregulation. In addition, a better progression-free survival (PFS) is associated with MGMT methylation and GTR but not with MGMT IHC and miRNA expression. In conclusion, our data reinforce the clinical relevance of miRNA expression as an additional marker to predict efficacy of chemoradiation in GBM.

Introduction: Walking while texting can create gait disturbances that may increase fall risk, especially in outdoors environment. To date, no study has quantified the effect of texting on motor behavior using different dynamic tasks in outdoor environments. We aimed to explore the impact of texting on dynamic tasks in indoor and outdoor environments., Methods: Twenty participants (age 38.3 ± 12.5 years, 12 F) had a Delsys inertial sensor fixed on their back and completed walk, turn, sit-to-stand, and stand-to-sit subtasks with and without texting in both indoor and outdoor environments., Results: While there was no difference in texting accuracy ( p = 0.3), there was a higher dual-tasking cost in walking time with texting outdoors than indoors ( p = 0.008)., Discussion: Dual tasking has a greater impact on walking time outdoors compared to an indoor environment. Our findings highlight the importance of patient education concerning dual-tasking and pedestrian safety in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Almajid, Appiah-Kubi, Cipriani and Goel.)

Smartphone applications are increasingly being used to measure gait due to their portability and cost-effectiveness. Important reliability metrics are not available for most of these devices. The purpose of this article was to evaluate the test-retest reliability and concurrent validity of spatiotemporal gait using the novel Gait Analyzer smartphone application compared to the Tekscan Strideway. Healthy participants (n=23) completed 12 trials of 10-meter walking, at two separate time points, using Gait Analyzer and while walking across the Tekscan Strideway. The results suggest excellent test-retest reliability for the Gait Analyzer and good test-retest reliability for the Tekscan Strideway for both velocity and cadence. At both time points, these devices were moderately to strongly correlated to one another for both velocity and cadence. These data suggest that the Gait Analyzer and Tekscan Strideway are reliable over time and can comparably calculate velocity and cadence., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background:   Listeria monocytogenes is an opportunistic gram-positive, facultative intracellular bacterium that causes invasive diseases mostly in pregnant women and immunosuppressed patients. Despite the predilection toward the central nervous system (CNS), it usually causes meningitis and meningoencephalitis, whereas brain abscesses are very uncommon., Case Presentation:  We describe the case of a 69-year-old homeless patient with a brain abscess due to L. monocytogenes who was successfully treated surgically by a guided stereotactic aspiration and antibiotic therapy with ampicillin and gentamicin. Our patient was discharged after 4 weeks of therapy without neurologic deficits. Additionally, we provide a review of the literature of brain abscesses caused by L. monocytogenes ., Conclusions:  This case highlights the need to drain cerebral abscesses and culture pus to correctly treat patients with antibiotics, especially given the high mortality rate of this infectious entity., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Glioblastoma is the most common and the most challenging to treat adult primary central nervous system tumor. Although modern management strategies modestly improved the overall survival, the prognosis remains dismal associated with poor life quality and the clinical course often dotted by treatment side effects and cognitive decline. Functional deterioration might be caused by obstructive or communicating hydrocephalus but due to poor overall prognosis surgical treatment options are often limited and its optimal management strategies remain elusive. We aimed to investigate risk factors, treatment options and outcomes for tumor-associated hydrocephalus in a contemporary 10 years cohort of glioblastoma patients., Methods: We reviewed electronic health records of 1800 glioblastoma patients operated at the Department of Neurosurgery, Medical Center - University of Freiburg from 2009 to 2019. Demographics, clinical characteristics and radiological features were analyzed. Univariate analysis for nominal variables was performed either by Fisher's exact test or Chi-square test, as appropriate., Results: We identified 39 glioblastoma patients with symptomatic communicating hydrocephalus treated by ventricular shunting (incidence 2.1%). Opening of the ventricular system during a previous tumor resection was associated with symptomatic hydrocephalus (p<0.05). There was also a trend toward location (frontal and temporal) and larger tumor volume. Number of craniotomies before shunting was not considered as a risk factor. Shunting improved hydrocephalus symptoms in 95% of the patients and Karnofsky Performance Score (KPS) could be restored after shunting. Of note, 75% of the patients had a post-shunting oncological treatment such as radiotherapy or chemotherapy, most prevalently chemotherapy. Infection (7.7%) and over- or under drainage (17.9%) were the most common complications requiring shunt revision in ten patients (25.6%), No peritoneal metastasis was found. The median overall survival (OS) was 385 days and the median post shunting survival was 135 days., Conclusion: Ventricular system opening was identified as a risk factor for communicating hydrocephalus in glioblastoma patients. Although glioblastoma treatment remains challenging, shunting improved hydrocephalus-related functional status and may be considered even in a palliative setting for symptom relief., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 El Rahal, Cipriani, Fung, Hohenhaus, Sveikata, Straehle, Shah, Heiland, Beck and Schnell.)

Background: Recent studies suggest that the prevalence of cardiac involvement in young competitive athletes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears to be low., Aim: This study aimed to determine the prevalence of cardiovascular involvement in young competitive athletes., Methods: In this single-center retrospective cohort study from one Division I university; we assessed the prevalence of cardiovascular involvement among collegiate athletes who tested positive for SARS-CoV-2 by polymerase chain reaction testing. Data were collected from June 25, 2020, to May 15, 2021. The primary outcome was the prevalence of cardiac involvement based on a comparison of pre- and post-infection electrocardiogram (ECGs). The secondary outcome was to evaluate for any association between ethnicity and the presence or absence of symptoms., Results: Among 99 athletes who tested positive for the SARS-CoV-2 virus (mean age 19.9 years [standard deviation 1.7 years]; 31% female), baseline ECG changes suggestive of cardiovascular involvement post-infection were detected in two athletes (2/99; 2%). There was a statistically significant association between ethnicity and the presence or absence of symptoms, χ 2 (3, n = 99) = 10.61, P = 0.01., Conclusions: The prevalence of cardiovascular involvement among collegiate athletes following SARS-CoV-2 infection in this cohort is low. Afro-American and Caucasian athletes are more likely to experience symptoms following SARS-CoV-2 infection in comparison to Hispanic and Pacific Islander athletes; however, there is no association between ethnicity and symptom severity., Relevance for Patients: These data add to the growing body of the literature and agree with larger cohorts that the risk of cardiac involvement post-infection appears to be low among elite athletic and semi-professional athletic populations., Competing Interests: Dr. Murray received payments during the project from NIH grant: P20GM103650. All other authors declare no conflict of interest., (Copyright: © Whioce Publishing Pte. Ltd.)

Background: It is currently unknown what specific neuronal deficits influence postural instability following SRC; however, the modulation of postural control relies heavily on the appropriate integration of sensory information from the visual, vestibular, and somatosensory system. It is possible symptom provocation of vestibular or ocular function is related to unsteady gait patterns during tandem gait., Aim: The purpose of this study was to evaluate the differences in temporal and center of pressure (CoP) metrics during discrete events of instrumented tandem gait (iTG) among those with sport-related concussion (SRC) compared to healthy controls. Secondarily, this study attempted to evaluate the relationship between iTG CoP metrics and the Vestibular/Ocular Motor Screening (VOMS) Exam., Materials and Methods: 30 collegiate athletes with SRC and 30 healthy controls completed three single task (ST) iTG trials on an instrumented walkway and the VOMS. All individuals with SRC were assessed within 24-48 h post-injury while all controls were measured during pre-participation physicals. CoP metrics in the anteroposterior (AP) and mediolateral (ML) directions and time to completion were evaluated during the first, turn and second pass of iTG between groups. VOMS score was correlated to the CoP metrics across the discrete events., Results: Athletes with SRC took longer to complete tandem gait ( P <0.001) along with the first pass, second pass but not the turn when compared to the control group. SRC had slower velocity in the AP direction during both the first ( P <0.001) and second pass ( P <0.001) with increased postural sway in the ML direction during the first pass ( P =0.014). During the turn, athletes with SRC had postural sway in the ML direction ( P =0.008). Finally, VOMS score was weakly negatively related to CoP velocity in the AP direction during first ( r =-0.39) and second (r=-0.36) pass while being weakly positively related to postural sway during the turn ( r =-0.30)., Conclusions: Athletes with SRC adopted a more conservative walking pattern and the presence of vestibular and/or ocular symptoms influence the ability to perform heel-to-toe walking., Relevance for Patients: Individuals with SRC will walk slower during heel-to-toe walking and move more in the ML direction with great movement in the ML direction while en pointe turning. This may increase given the total amount of vestibular or vision symptoms following the SRC., Competing Interests: None of the authors have any professional relationships with companies that may benefit from this publication. Unrelated to this work, Dr. Howell has received research support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03HD094560), the National Institute of Neurological Disorders and Strokes (R01NS100952, R03HD094560, and R43NS108823), and MINDSOURCE Brain Injury Network., (Copyright: © Whioce Publishing Pte. Ltd.)

Background: Glioblastoma of the corpus callosum (ccGBM) are rare tumors, with a dismal prognosis marked by a rapid clinical deterioration. For a long time, surgical treatment was not considered beneficial for most patients with such tumors. Recent studies claimed an improved survival for patients undergoing extensive resection, albeit without integration of the molecular profile of the lesions. The purpose of this study was to investigate the effect of biopsy and surgical resection on oncological and functional outcomes in patients with IDH wild-type ccGBM., Methods: We performed a retrospective analysis of our institution's database of patients having been treated for high-grade glioma between 2005 and 2017. Inclusion criteria were defined as follows: patients older than 18 years, histopathological, and molecularly defined IDH wild-type glioma, major tumor mass (at least 2/3) invading the corpus callosum in the sagittal plane with a uni- or bilateral infiltration of the adjacent lobules. Surgical therapy (resection vs. biopsy), extent of resection according to the remaining tumor volume and adjuvant treatment as well as overall survival and functional outcome using the Karnofsky Performance Score (KPS) were analyzed., Results: Fifty-five patients were included in the study, from which the mean age was 64 years and men (n = 34, 61.8%) were more often affected than women (n = 21, 38.2%). Thirty (54.5%) patients were treated with stereotactic biopsy alone, while 25 patients received tumor resection resulting in 14.5% (n = 8) gross-total resections and 30.9% (n = 17) partial resections. The 2-year survival rate after resection was 30% compared to 7% after biopsy (p = 0.047). The major benefit was achieved in the group with gross-total resection, while partial resection failed to improve survival. Neurological outcome measured by KPS did not differ between both groups either pre- or postoperatively., Conclusions: Our study suggests that in patients with corpus callosum glioblastoma, gross-total resection prolongs survival without negatively impacting neurological outcome as compared to biopsy.

Background: Oligodendroglioma (ODG) are CNS resistant tumors characterized by their unique molecular signature, namely a combined deletion of 1p and 19q simultaneously to an IDH1/2 mutation. These tumors have a more favorable clinical outcome compared to other gliomas and a long-time survival that ranges between 10 and 20 years. However, during the course of the disease, multiple recurrences occur and the optimal treatment at each stage of the disease remains unclear. Here we report a retrospective longitudinal observation study of 836 MRI examinations in 44 ODG patients., Methods: We quantified the volume of T2-hyperintensity to compute growth behavior in dependence of different treatment modalities, using various computational models., Results: The identified growth pattern revealed dynamic changes, which were found to be patient-specific an did not correlate with clinical parameter or therapeutic interventions. Further, we showed that, surgical resection is beneficial for overall survival regardless the WHO grad or timepoint of surgery. To improve overall survival, an extent of resection above 50% is required. Multiple resections do not generally improve overall survival, except a greater extent of resection than in previous surgeries was achieved., Conclusions: Our data aids to improve the interpretation of MRI images in clinical practice.

Objective: With global aging, elective craniotomies are increasingly being performed in elderly patients. There is a paucity of prospective studies evaluating the impact of these procedures on the geriatric population. The goal of this study was to assess the safety of elective craniotomies for elderly patients in modern neurosurgery., Methods: For this cohort study, adult patients, who underwent elective craniotomies between November 1, 2011, and October 31, 2018, were allocated to 3 age groups (group 1, < 65 years [n = 1008], group 2, ≥ 65 to < 75 [n = 315], and group 3, ≥ 75 [n = 129]). Primary outcome was the 30-day mortality after craniotomy. Secondary outcomes included rate of delayed extubation (> 1 hour), need for emergency head CT scan and reoperation within 48 hours after surgery, length of postoperative intensive or intermediate care unit stay, hospital length of stay (LOS), and rate of discharge to home. Adjustment for American Society of Anesthesiologists Physical Status (ASA PS) class, estimated blood loss, and duration of surgery were analyzed as a comparison using multiple logistic regression. For significant differences a post hoc analysis was performed., Results: In total, 1452 patients (mean age 55.4 ± 14.7 years) were included. The overall mortality rate was 0.55% (n = 8), with no significant differences between groups (group 1: 0.5% [95% binominal CI 0.2%, 1.2%]; group 2: 0.3% [95% binominal CI 0.0%, 1.7%]; group 3: 1.6% [95% binominal CI 0.2%, 5.5%]). Deceased patients had a significantly higher ASA PS class (2.88 ± 0.35 vs 2.42 ± 0.62; difference 0.46 [95% CI 0.03, 0.89]; p = 0.036) and increased estimated blood loss (1444 ± 1973 ml vs 436 ± 545 ml [95% CI 618, 1398]; p <0.001). Significant differences were found in the rate of postoperative head CT scans (group 1: 6.65% [n = 67], group 2: 7.30% [n = 23], group 3: 15.50% [n = 20]; p = 0.006), LOS (group 1: median 5 days [IQR 4; 7 days], group 2: 5 days [IQR 4; 7 days], and group 3: 7 days [5; 9 days]; p = 0.001), and rate of discharge to home (group 1: 79.0% [n = 796], group 2: 72.0% [n = 227], and group 3: 44.2% [n = 57]; p < 0.001)., Conclusions: Mortality following elective craniotomy was low in all age groups. Today, elective craniotomy for well-selected patients is safe, and for elderly patients, too. Elderly patients are more dependent on discharge to other hospitals and postacute care facilities after elective craniotomy. Clinical trial registration no.: NCT01987648 (clinicaltrials.gov).

Context: Lower extremity musculoskeletal (LEMSK) injury may be more prevalent among those with a history of sport-related concussion (SRC)., Objective: To investigate the relationship between baseline postural control metrics and the LEMSK injury incidence in National Collegiate Athletic Association Division I student-athletes with a history of SRC., Setting: National Collegiate Athletic Association Division I athletes., Design: Cohort study., Patients or Other Participants: Of 84 total athletes (62 males), 42 had been previously diagnosed with an SRC, and 42 were matched controls based on age, sex, height, weight, and sport., Main Outcome Measure(s): During the preseason baseline evaluation, all participants performed 3 trials of eyes-open and eyes-closed upright quiet stance on a force platform. Medical charts were assessed for all the LEMSK injuries that occurred from preseason baseline to 1 year later. Center-of-pressure data in the anteroposterior and mediolateral directions were filtered before we calculated root mean square and mean excursion velocity; the complexity index was calculated from the unfiltered data. Factorial analysis-of-variance models were used to examine differences between groups and across conditions for root mean square; mean excursion velocity, complexity index, and tests of association to examine between-groups LEMSK differences; and logistic regression models to predict LEMSK., Results: Concussion history and injury incidence were related in the SRC group ( P = .043). The complexity index of the SRC group was lower with eyes closed (14.08 ± 0.63 versus 15.93 ± 0.52) and eyes open (10.25 ± 0.52 vs 11.80 ± 0.57) in the mediolateral direction than for the control participants ( P < .05). Eyes-open root mean square in the mediolateral direction was greater for the SRC group (5.00 ± 0.28 mm) than the control group (4.10 ± 0.22 mm). Logistic regression models significantly predicted LEMSK only in control participants., Conclusions: These findings may suggest that LEMSK after SRC cannot be predicted from postural-control metrics at baseline.

Object: The treatment of choice in glioblastoma (GBM) is the maximal surgical extent of resection (EOR) followed by adjuvant chemo-radiotherapy. Furthermore, methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with prolonged overall survival (OS) and progression free survival (PFS). The objective of the present study is correlate the biomolecular aspects in relation with EOR. Materials and methods: We analyzed a series of 116 patients with IDH-1 wild type GBM and different EOR (Gross Total Resection-GTR-, Partial Resection-PR- and Biopsy), treated with adjuvant chemo-radiotherapy. The MGMT status was analyzed in terms of promoter methylation and protein expression. Results: When GTR was possible, OS and PFS were significantly better compared to the other two groups ( p = 0.001 and p = 0.035, respectively). MGMT methylation was significantly associated with better OS in the biopsy group ( p = 0.022) and better OS and PFS in PR ( p = 0.02 and p = 0.012, respectively), but not in the GTR group ( p = 0.252 for OS, p = 0.256 for PFS) nor the PFS in the biopsy group ( p = 0.259). MGMT protein expression levels do not show any association with OS and PFS, regardless of the type of surgery. Conclusions: Our study confirms the positive association of a safe maximal EOR with better OS and PFS, and indicates a positive prognostic value of MGMT methylation status only in case of the presence of residual tumor tissue. MGMT protein expression seems not to play a clinical role in relation with the type of surgery., (Copyright © 2020 Marchi, Sahnane, Cerutti, Cipriani, Barizzi, Stefanini, Epistolio, Cerati, Balbi, Mazzucchelli, Sessa, Pesce, Reinert and Frattini.)

Introduction: Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients., Materials and Methods: We included a cohort of 39 elderly patients (> 65 years) with a second resection as treatment option in the case of a tumor recurrence. A causal inference model was built by multiple non- and semiparametric models, which was used to identify matched patients from our elderly GBM database which comprises 538 patients. The matched cohorts were analyzed by a Cox-regression model adjusted by time-dependent covariates., Results: The Cox-regression analysis showed a significant survival benefit (Hazard Ratio: 0.6, 95% CI 0.36-0.9, p-value = 0.0427) for the re-resected group (18.0 months, 95% CI 13.97-23.2 months) compared to the group without re-resection (10.1 months, 95% CI 8.09-20.9 months). No differences in the co-morbidities or hemato-oncological side effects during chemotherapy could be detected. Anesthetic- and surgical complications were rare and comparable to the complication rate of patients undergoing the first-line resection., Conclusion: Taken together, in elderly patients, re-resection is an acceptable treatment option in the recurrent state of a glioblastoma. The individual evaluation of the patients' medical status as well as the chances of withstanding general anesthesia needs to be done in close interdisciplinary consultation. If these requirements are met, elderly patients benefit from a re-resection.

Background: Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects., Methods: Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter., Results: Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches., Conclusion: This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes., Competing Interests: The authors have declared that no competing interests exist.

Objective: Spontaneous intracranial hypotension is caused by spinal cerebrospinal fluid leakage. Patients with orthostatic headaches and cerebrospinal fluid leakage show a decrease in optic nerve sheath diameter upon movement from supine to upright position. We hypothesized that the decrease in optic nerve sheath diameter upon gravitational challenge would cease after closure of the leak., Methods: We included 29 patients with spontaneous intracranial hypotension and refractory symptoms admitted from 2013 to 2016. The systematic workup included: Optic nerve sheath diameter sonography, spinal MRI and dynamic myelography with subsequent CT. Microsurgical sealing of the cerebrospinal fluid leak was the aim in all cases., Results: Of 29 patients with a proven cerebrospinal fluid leak, one declined surgery. A single patient was lost to follow-up. In 27 cases, the cerebrospinal fluid leak was successfully sealed by microsurgery. The width of the optic nerve sheath diameter in supine position increased from 5.08 ± 0.66 mm before to 5.36 ± 0.53 mm after surgery ( p = 0.03). Comparing the response of the optic nerve sheath diameter to gravitational challenge, there was a significant change from before (-0.36 ± 0.32 mm) to after surgery (0.00 ± 0.19 mm, p < 0.01). In parallel, spontaneous intracranial hypotension-related symptoms resolved in 26, decreased in one and persisted in a single patient despite recovery of gait., Conclusions: The sonographic assessment of the optic nerve sheath diameter with gravitational challenge can distinguish open from closed spinal cerebrospinal fluid fistulas in spontaneous intracranial hypotension patients. A response to the gravitational challenge, that is, no more collapse of the optic nerve sheath while standing up, can be seen after successful treatment and correlates with the resolution of clinical symptoms. Sonography of the optic nerve sheath diameter may be utilized for non-invasive follow-up in spontaneous intracranial hypotension.

Intrinsic motivations drive the acquisition of knowledge and skills on the basis of novel or surprising stimuli or the pleasure to learn new skills. In so doing, they are different from extrinsic motivations that are mainly linked to drives that promote survival and reproduction. Intrinsic motivations have been implicitly exploited in several psychological experiments but, due to the lack of proper paradigms, they are rarely a direct subject of investigation. This article investigates how different intrinsic motivation mechanisms can support the learning of visual skills, such as "foveate a particular object in space", using a gaze contingency paradigm. In the experiment participants could freely foveate objects shown in a computer screen. Foveating each of two "button" pictures caused different effects: one caused the appearance of a simple image (blue rectangle) in unexpected positions, while the other evoked the appearance of an always-novel picture (objects or animals). The experiment studied how two possible intrinsic motivation mechanisms might guide learning to foveate one or the other button picture. One mechanism is based on the sudden, surprising appearance of a familiar image at unpredicted locations, and a second one is based on the content novelty of the images. The results show the comparative effectiveness of the mechanism based on image novelty, whereas they do not support the operation of the mechanism based on the surprising location of the image appearance. Interestingly, these results were also obtained with participants that, according to a post experiment questionnaire, had not understood the functions of the different buttons suggesting that novelty-based intrinsic motivation mechanisms might operate even at an unconscious level.