Frailty indices predict mortality, complications and functional improvements in supratentorial meningioma patients over 80 years of age.

PURPOSE: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years. METHODS: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery. RESULTS: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2)). CONCLUSION: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement.

Acute-to-chronic subdural hematoma: radiographic and clinical progression from acute subdural hematoma.

INTRODUCTION: The pathogenesis of chronic subdural hematoma (CSDH) has not been completely understood. However, different mechanisms can result in space-occupying subdural fluid collections, one pathway can be the transformation of an original trauma-induced acute subdural hematoma (ASDH) into a CSDH. MATERIALS AND METHODS: All patients with unilateral CSDH, requiring burr hole trephination between 2018 and 2023 were included. The population was distributed into an acute-to-chronic group (group A, n = 41) and into a conventional group (group B, n = 282). Clinical and radiographic parameters were analyzed. In analysis A, changes of parameters after trauma within group A are compared. In analysis B, parameters between the two groups before surgery were correlated. RESULTS: In group A, volume and midline shift increased significantly during the progression from acute-to-chronic (p < 0.001, resp.). Clinical performance (modified Rankin scale, Glasgow Coma Scale) dropped significantly (p = 0.035, p < 0.001, resp.). Median time between trauma with ASDH and surgery for CSDH was 12 days. Patients treated up to the 12th day presented with larger volume of ASDH (p = 0.012). Before burr hole trephination, patients in group A presented with disturbance of consciousness (DOC) more often (p = 0.002), however less commonly with a new motor deficit (p = 0.014). Despite similar midline shift between the groups (p = 0.8), the maximal hematoma width was greater in group B (p < 0.001). CONCLUSION: If ASDH transforms to CSDH, treatment may become mandatory early due to increase in volume and midline shift. Close monitoring of these patients is crucial since DOC and rapid deterioration is common in this type of SDH.

Risk factors for prolonged length of stay after first single-level lumbar microdiscectomy.

OBJECTIVE: The objective is to identify risk factors that potentially prolong the hospital stay in patients after undergoing first single-level open lumbar microdiscectomy. METHODS: A retrospective single-centre study was conducted. Demographic data, medical records, intraoperative course, and imaging studies were analysed. The outcome measure was defined by the number of days stayed after the operation. A prolonged length of stay (LOS) stay was defined as a minimum of one additional day beyond the median hospital stay in our patient collective. Bivariate analysis and multiple stepwise regression were used to identify independent factors related to the prolonged hospital stay. RESULTS: Two hundred consecutive patients who underwent first lumbar microdiscectomy between 2018 and 2022 at our clinic were included in this study. Statistical analysis of factors potentially prolonging postoperative hospital stay was done for a total of 24 factors, seven of them were significantly related to prolonged LOS in bivariate analysis. Sex (p = 0.002, median 5 vs. 4 days for females vs. males) and age (rs = 0.35, p ≤ 0.001, N = 200) were identified among the examined demographic factors. Regarding preoperative physical status, preoperative immobility reached statistical significance (p ≤ 0.001, median 5 vs. 4 days). Diabetes mellitus (p = 0.043, median 5 vs. 4 days), anticoagulation and/or antiplatelet agents (p = 0.045, median 5 vs. 4 days), and postoperative narcotic consumption (p ≤ 0.001, median 5 vs. 4 days) as comorbidities were associated with a prolonged hospital stay. Performance of nucleotomy (p = 0.023, median 5 vs. 4 days) was a significant intraoperative factor. After linear stepwise multivariable regression, only preoperative immobility (p ≤ 0.001) was identified as independent risk factors for prolonged length of postoperative hospital stay. CONCLUSION: Our study identified preoperative immobility as a significant predictor of prolonged hospital stay, highlighting its value in preoperative assessments and as a tool to pinpoint at-risk patients. Prospective clinical trials with detailed assessment of mobility, including grading, need to be done to verify our results.

Tumor-Specific Alterations in Motor Cortex Excitability and Tractography of the Corticospinal Tract-A Navigated Transcranial Magnetic Stimulation Study.

BACKGROUND: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. METHODS: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance - LTD) were measured. RESULTS: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p < 0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). CONCLUSIONS: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas.

Embolization of the middle meningeal artery vs. second surgery-treatment response and volume course of recurrent chronic subdural hematomas.

BACKGROUND: Despite multiple studies on the embolization of the middle meningeal artery, there is limited data on the treatment response of recurrent chronic subdural hematomas (CSDH) to embolization and on the volume change. METHODS: We retrospectively compared the treatment response and volume change of recurrent CSDHs in a conventional group (second surgery) with an embolization group (embolization as stand-alone treatment) during the time-period from August 2019 until June 2022. Different clinical and radiological factors were assessed. Treatment failure was defined as necessity of treatment for second recurrence. Hematoma volumes were determined in the initial CT scan before first surgery, after the first surgery, before retreatment as well as in an early (1 day-2 weeks) and in a late follow-up CT scan (2-8 weeks). RESULTS: Fifty recurrent hematomas after initial surgery were treated either by second surgery (n = 27) or by embolization (n = 23). 8/27 (26,6%) surgically treated and 3/23 (13%) of the hematomas treated by embolization needed to be treated again. This leads to an efficacy in recurrent hematomas of 73,4% in surgically treated and of 87% in embolized hematomas (p = 0.189). In the conventional group, mean volume decreased significantly already in the first follow-up CT scan from 101.7 ml (SD 53.7) to 60.7 ml (SD 40.3) (p = 0.001) and dropped further in the later follow-up scan to 46.6 ml (SD 37.1) (p = 0.001). In the embolization group, the mean volume did decrease insignificantly from 75.1 ml (SD 27.3) to 68 ml (SD 31.4) in the first scan (p = 0.062). However, in the late scan significant volume reduction to 30.8 ml (SD 17.1) could be observed (p = 0.002). CONCLUSIONS: Embolization of the middle meningeal artery is an effective treatment option for recurrent CSDH. Patients with mild symptoms who can tolerate slow volume reduction are suitable for embolization, whereas patients with severe symptoms should be reserved for surgery.

Factors which influence the complications of external ventricular cerebrospinal fluid drainage.

BACKGROUND: External ventricular drainage (EVD) is one of the most common neurosurgical procedures in emergencies. This study aims to find out which factors influence the occurrence of EVD-related complications in a comparative investigation of metal needles and polyurethane catheters. This is the first clinical study comparing these two systems. METHODS: Adult patients undergoing pre-coronal EVD placement via freehand burr hole trepanation were included in this prospective study. The exclusion criteria were the open EVD insertion and/or a pre-existing infectious disease of the central nervous system. RESULTS: Two hundred consecutive patients were enrolled. Of these, 100 patients were treated by using metal EVD (group 1) and 100 patients with polyurethane catheters (group 2). The overall complication rate was 26% (misplacement 13.5%, hemorrhage 12.5%, infection 2.5%, and dislocation 1%) without statistically significant differences between both groups. Generalized brain edema and midline shift had a significant influence on misplacements (generalized brain edema: p = 0.0002, Cramer-V: 0.307, OR = 7.364, 95% CI: 2.691-20.148; all patients: p = 0.001, Cramer-V: 0.48, OR = 43.5, 95% CI: 4.327-437.295; group 1: p = 0.047, Cramer-V: 0.216, OR = 3.75, 95% CI: 1.064-13.221; group 2: midline shift: p = 0.038, Cramer-V: 0.195, OR = 3.626, 95% CI: 1.389-9.464) all patients: p = 0.053, Cramer-V: 0.231, OR = 5.533, 95% CI 1.131-27.081; group 1: p = 0.138, Cramer-V: 0.168, OR = 2.769, 95% CI: 0.813-9.429 group 2. Hemorrhages were associated with the use of oral anticoagulants or antiplatelet therapy (p = 0.002; Cramer-V: 0.220, OR = 3.798, 95% CI: 1.572-9.175) with a statistically similar influence in both groups. CONCLUSION: Generalized brain edema has a significant influence on misplacements in both groups. Midline shift lost its significance when considering only the patients in group 2. Patients under oral anticoagulation and antiplatelet therapy have increased odds of EVD-associated hemorrhage. Metal needles and polyurethane catheters are equivalent in terms of patient safety when there are no midline shift and generalized brain edema.

Neurocritical care complications and interventions influence the outcome in aneurysmal subarachnoid hemorrhage.

BACKGROUND: This observational study was performed to show the impact of complications and interventions during neurocritical care on the outcome after aneurysmal subarachnoid hemorrhage (SAH). METHODS: We analyzed 203 cases treated for ruptured intracranial aneurysms, which were classified regarding clinical outcome after one year according to the modified Rankin Scale (mRS). We reviewed the data with reference to the occurrence of typical complications and interventions in neurocritical care units. RESULTS: Decompressive craniectomy (odds ratio 21.77 / 6.17 ; p < 0.0001 / p = 0.013), sepsis (odds ratio 14.67 / 6.08 ; p = 0.037 / 0.033) and hydrocephalus (odds ratio 3.71 / 6.46 ; p = 0.010 / 0.00095) were significant predictors for poor outcome and death after one year beside "World Federation of Neurosurgical Societies" (WFNS) grade (odds ratio 3.86 / 4.67 ; p < 0.0001 / p < 0.0001) and age (odds ratio 1.06 / 1.10 ; p = 0.0030 / p < 0.0001) in our multivariate analysis (binary logistic regression model). CONCLUSIONS: In summary, decompressive craniectomy, sepsis and hydrocephalus significantly influence the outcome and occurrence of death after aneurysmal SAH.

Spontaneous disappearance of a spinal dural arteriovenous fistula.

We report a case of an unusual spontaneous obliteration of a spinal dural arteriovenous fistula after diagnosis confirmation through spinal angiography. To our knowledge, there are only two previously documented cases of spontaneous disappearance of non-traumatic spinal dural arteriovenous fistulas.

Microsurgical posterior cervical foraminotomy: a study of 181 cases.

BACKGROUND: An unsettled controversy over the appropriate surgical approach in cases of cervical radiculopathy caused by degenerative vertebrae and intervertebral discs is still present. The purpose of this study is to examine the efficacy of microsurgical posterior foraminotomy in the treatment of cervical radiculopathy and to find out whether the underlying pathology (soft disc herniation/spondylosis) is of value in predicting long-term outcome after this procedure. METHODS: Patients, who underwent posterior cervical foraminotomy (PCF) at our department between 2006 and 2013 for unilateral mono-segmental lateral soft disc herniation, or spondylosis, or both, were enrolled in this study. Demographic, clinical and surgical data were retrospectively reviewed. The patients were subsequently interviewed by telephone to identify their long-term outcome. The clinical outcomes were evaluated using Odom's criteria. Descriptive statistics were frequencies and percentage of occurrence for categorical variables and mean and range for continuous variables. RESULTS: One hundred eighty-one patients were included in this study, with a median follow-up of 58 months (mean 43 months, range 12-96 months). The overall re-operation rate was 7.2% (13 patients); 11 patients (6%) for recurrent root symptoms due to recurrent disc herniation (six patients, 3.3%) and re-stenosis (five patients, 2.8%), one patient (0.55%) for wound infection and one patient (0.55%) for postoperative haematoma. Among the eleven patients who underwent re-operation for recurrent root symptoms there was one patient who additionally had persistent cerebrospinal fluid leak and superficial posterior wound infection. There was no significant difference between lateral soft disc herniation and spondylosis in term of re-operation rate. At discharge, excellent or good outcome was achieved in 89% of patients; the long-term success rate was 97.2% using Odom's criteria. CONCLUSION: Microsurgical PCF is an effective technique for treating lateral spinal root compression. Proper patient selection is obligatory to achieve the best results.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. METHODS: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. RESULTS: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Significance of navigated transcranial magnetic stimulation and tractography to preserve motor function in patients undergoing surgery for motor eloquent gliomas.

Resection of gliomas in or close to motor areas is at high risk for morbidity and development of surgery-related deficits. Navigated transcranial magnetic stimulation (nTMS) including nTMS-based tractography is suitable for presurgical planning and risk assessment. The aim of this study was to investigate the association of postoperative motor status and the spatial relation to motor eloquent brain tissue in order to increase the understanding of postoperative motor deficits. Patient data, nTMS examinations and imaging studies were retrospectively reviewed, corticospinal tracts (CST) were reconstructed with two different approaches of nTMS-based seeding. Postoperative imaging and nTMS-augmented preoperative imaging were merged to identify the relation between motor positive cortical and subcortical areas and the resection cavity. 38 tumor surgeries were performed in 36 glioma patients (28.9% female) aged 55.1 ± 13.8 years. Mean distance between the CST and the lesion was 6.9 ± 5.1 mm at 75% of the patient-individual fractional anisotropy threshold and median tumor volume reduction was 97.7 ± 11.6%. The positive predictive value for permanent deficits after resection of nTMS positive areas was 66.7% and the corresponding negative predictive value was 90.6%. Distances between the resection cavity and the CST were higher in patients with postoperative stable motor function. Extent of resection and distance between resection cavity and CST correlated well. The present study strongly supports preoperative nTMS as an important surgical tool for preserving motor function in glioma patients at risk.

Resection of meningiomas located in motor eloquent areas - comparative analysis of navigated transcranial magnetic stimulation and conventional neuronavigation.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) has been established as a preoperative diagnostic procedure in glioma surgery, increasing the extent of resection and preserving functional outcome. nTMS motor mapping for the resection of motor eloquent meningiomas has not been evaluated in a comparative analysis, yet. METHODS: We conducted a retrospective matched-pair analysis for tumor location and size in meningioma patients with tumors located over or close to the primary motor cortex. Half of the study population received nTMS motor mapping preoperatively (nTMS-group). The primary endpoint were permanent surgery-related motor deficits. Additional factors associated with new motor deficits were evaluated apart from nTMS. RESULTS: 62 patients (mean age 62 ± 15.8 years) were evaluated. 31 patients received preoperative nTMS motor mapping. In this group, motor thresholds (rMT) corresponded with tumor location and preoperative motor status, but could not predict motor outcome. No patient with preoperative intact motor function had a surgery-related permanent deficit in the nTMS group whereas four patients in the non-TMS group with preoperative intact motor status harbored from permanent deficits. 13 patients (21.3%) had a permanent motor deficit postoperatively with no difference between the nTMS and the non-TMS-group. Worsening in motor function was associated with higher patient age (p = 0.01) and contact to the superior sagittal sinus (p = 0.027). CONCLUSION: nTMSmotor mapping did not lead to postoperative preservation in motorfunction. nTMS data corresponded well with the preoperative motorstatus and were associated with postoperative permanent deficits if tumors were located over the motor hotspot according to nTMS.

Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.

BACKGROUND AND OBJECTIVES: Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm 3 ), medium (10-50 cm 3 ), and large (>50 cm 3 ). RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm 3 ; large PTBE volume correlated with poor preoperative KPS status ( P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

Glial Glutamate Transporter-Mediated Plasticity: System xc-/xCT/SLC7A11 and EAAT1/2 in Brain Diseases.

Glial cells play an essential role in the complex function of the nervous system. In particular, astrocytes provide nutritive support for neuronal cells and are involved in regulating synaptic transmission. Oligodendrocytes ensheath axons and support information transfer over long distances. Microglial cells constitute part of the innate immune system in the brain. Glial cells are equipped with the glutamate-cystine-exchanger xCT (SLC7A11), the catalytic subunit of system xc-, and the excitatory amino acid transporter 1 (EAAT1, GLAST) and EAAT2 (GLT-1). Thereby, glial cells maintain balanced extracellular glutamate levels that enable synaptic transmission and prevent excitotoxic states. Expression levels of these transporters, however, are not fixed. Instead, expression of glial glutamate transporters are highly regulated in reaction to the external situations. Interestingly, such regulation and homeostasis is lost in diseases such as glioma, (tumor-associated) epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis or multiple sclerosis. Upregulation of system xc- (xCT or SLC7A11) increases glutamate export from the cell, while a downregulation of EAATs decreases intracellular glutamate import. Occurring simultaneously, these reactions entail excitotoxicity and thus harm neuronal function. The release of glutamate via the antiporter system xc- is accompanied by the import of cystine-an amino acid essential in the antioxidant glutathione. This homeostasis between excitotoxicity and intracellular antioxidant response is plastic and off-balance in central nervous system (CNS) diseases. System xc- is highly expressed on glioma cells and sensitizes them to ferroptotic cell death. Hence, system xc- is a potential target for chemotherapeutic add-on therapy. Recent research reveals a pivotal role of system xc- and EAAT1/2 in tumor-associated and other types of epilepsy. Numerous studies show that in Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, these glutamate transporters are dysregulated-and disease mechanisms could be interposed by targeting system xc- and EAAT1/2. Interestingly, in neuroinflammatory diseases such as multiple sclerosis, there is growing evidence for glutamate transporter involvement. Here, we propose that the current knowledge strongly suggest a benefit from rebalancing glial transporters during treatment.

Influence of clinical and tumor-specific factors on the resting motor threshold in navigated transcranial magnetic stimulation.

OBJECTIVE: Preoperative non-invasive mapping of motor function with navigated transcranial magnetic stimulation (nTMS) has become a widely used diagnostic procedure. Determination of the patient-individual resting motor threshold (rMT) is of great importance to achieve reliable results when conducting nTMS motor mapping. Factors which contribute to differences in rMT of brain tumor patients have not been fully investigated. METHODS: We included adult patients with all types of de novo and recurrent intracranial lesions, suspicious for intra-axial brain tumors. The outcome measure was the rMT of the upper extremity, defined as the stimulation intensity eliciting motor evoked potentials with amplitudes greater than 50µV in 50 % of applied stimulations. RESULTS: Eighty nTMS examinations in 75 patients (37.5 % female) aged 57.9 ± 14.9 years were evaluated. In non-parametric testing, rMT values were higher in patients with upper extremity paresis (p = 0.024) and lower in patients with high grade gliomas (HGG) (p = 0.001). rMT inversely correlated with patient age (rs=-0.28, p = 0.013) and edema volume (rs=-0.28, p = 0.012) In regression analysis, infiltration of the precentral gyrus (p<0.001) increased rMT values. Values of rMT were reduced in high grade gliomas (p<0.001), in patients taking Levetiracetam (p = 0.019) and if perilesional edema infiltrated motor eloquent brain (p<0.001). Subgroup analyses of glioma patients revealed similar results. Values of rMT did not differ between hand and forearm muscles. CONCLUSION: Most factors confounding rMT in our study were specific to the lesion. These factors contributed to the variability in cortical excitability and must be considered in clinical work with nTMS to achieve reliable results with nTMS motor mapping.

Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.

Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguently, glutamate is also an excitatory neurotransmitter and evokes neuronal cell death at high concentrations. Even though glutamate signaling at the receptor and its downstream effectors has been extensively investigated at the molecular level, there has been little insight into how glutamate enters the tumor microenvironment and impacts on metabolic equilibration until recently. Surprisingly, the 12 transmembrane spanning tranporter xCT (SLC7A11) appeared to be a major player in this process, mediating glutamate secretion and ferroptosis. Also, PPARγ is associated with ferroptosis in neurodegeneration, thereby destroying neurons and causing brain swelling. Although these data are intriguing, tumor-associated edema has so far been quoted as of vasogenic origin. Hence, glutamate and PPARγ biology in the process of glioma-induced brain swelling is conceptually challenging. By inhibiting xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated. This review sheds light on the role of glutamate in brain tumors presenting the conceptual challenge that xCT disruption causes ferroptosis activation in malignant brain tumors. Thus, interfering with glutamate takes center stage in forming the basis of a metabolic equilibration approach.

Large diameter hemicraniectomy does not improve long-term outcome in malignant infarction.

INTRODUCTION: In malignant cerebral infarction decompressive hemicraniectomy has demonstrated beneficial effects, but the optimum size of hemicraniectomy is still a matter of debate. Some surgeons prefer a large-sized hemicraniectomy with a diameter of more than 14 cm (HC > 14). We investigated whether this approach is associated with reduced mortality and an improved long-term functional outcome compared to a standard hemicraniectomy with a diameter of less than 14 cm (HC ≤ 14). METHODS: Patients from the DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY) registry who received hemicraniectomy were dichotomized according to the hemicraniectomy diameter (HC ≤ 14 cm vs. HC > 14 cm). The primary outcome was modified Rankin scale (mRS) score ≤ 4 after 12 months. Secondary outcomes were in-hospital mortality, mRS ≤ 3 and mortality after 12 months, and the rate of hemicraniectomy-related complications. The diameter of the hemicraniectomy was examined as an independent predictor of functional outcome in multivariable analyses. RESULTS: Among 130 patients (32.3% female, mean (SD) age 55 (11) years), the mean hemicraniectomy diameter was 13.6 cm. 42 patients (32.3%) had HC > 14. There were no significant differences in the primary outcome and mortality by size of hemicraniectomy. Rate of complications did not differ (HC ≤ 14 27.6% vs. HC > 14 36.6%, p = 0.302). Age and infarct volume but not hemicraniectomy diameter were associated with outcome in multivariable analyses. CONCLUSION: In this post-hoc analysis, large hemicraniectomy was not associated with an improved outcome or lower mortality in unselected patients with malignant middle cerebral artery infarction. Randomized trials should further examine whether individual patients could benefit from a large-sized hemicraniectomy. CLINICAL TRIAL REGISTRATION INFORMATION: German Clinical Trials Register (URL: https://www.drks.de ; Unique Identifier: DRKS00000624).

Assessing the feasibility of mapping the tibialis anterior muscle with navigated transcranial magnetic stimulation in neuro-oncologic patients.

Mapping the lower extremity with navigated transcranial magnetic stimulation (nTMS) still remains challenging for the investigator. Clinical factors influencing leg mapping with nTMS have not been fully investigated yet. The aim of the study was to identify factors which influence the possibility of eliciting motor evoked potentials (MEPs) from the tibialis anterior muscle (TA). Patient records, imaging, nTMS examinations and tractography were retrospectively evaluated. 48 nTMS examinations were performed in 46 brain tumor patients. Reproducible MEPs were recorded in 20 patients (41.67%). Younger age (p = 0.044) and absence of perifocal edema (p = 0.035, Cramer's V = 0.34, OR = 0.22, 95% CI = 0.06-0.81) facilitated mapping the TA muscle. Leg motor deficit (p = 0.49, Cramer's V = 0.12, OR = 0.53, 95%CI = 0.12-2.36), tumor entity (p = 0.36, Cramer's V = 0.22), tumor location (p = 0.52, Cramer's V = 0.26) and stimulation intensity (p = 0.158) were no significant factors. The distance between the tumor and the pyramidal tract was higher (p = 0.005) in patients with successful mapping of the TA. The possibility to stimulate the leg motor area was associated with no postoperative aggravation of motor deficits in general (p = 0.005, Cramer's V = 0.45, OR = 0.63, 95%CI = 0.46-0.85) but could not serve as a specific predictor of postoperative lower extremity function. In conclusion, successful mapping of the TA muscle for neurosurgical planning is influenced by young patient age, absence of edema and greater distance to the CST, whereas tumor entity and stimulation intensity were non-significant.

Therapeutic Potential of Selenium in Glioblastoma.

Little progress has been made in the long-term management of malignant brain tumors, leaving patients with glioblastoma, unfortunately, with a fatal prognosis. Glioblastoma remains the most aggressive primary brain cancer in adults. Similar to other cancers, glioblastoma undergoes a cellular metabolic reprogramming to form an oxidative tumor microenvironment, thereby fostering proliferation, angiogenesis and tumor cell survival. Latest investigations revealed that micronutrients, such as selenium, may have positive effects in glioblastoma treatment, providing promising chances regarding the current limitations in surgical treatment and radiochemotherapy outcomes. Selenium is an essential micronutrient with anti-oxidative and anti-cancer properties. There is additional evidence of Se deficiency in patients suffering from brain malignancies, which increases its importance as a therapeutic option for glioblastoma therapy. It is well known that selenium, through selenoproteins, modulates metabolic pathways and regulates redox homeostasis. Therefore, selenium impacts on the interaction in the tumor microenvironment between tumor cells, tumor-associated cells and immune cells. In this review we take a closer look at the current knowledge about the potential of selenium on glioblastoma, by focusing on brain edema, glioma-related angiogenesis, and cells in tumor microenvironment such as glioma-associated microglia/macrophages.

Medulloblastoma in adults - reviewing the literature from a surgeon's point of view.

Medulloblastoma is a common primary brain tumor in children but it is a rare cancer in adult patients. We reviewed the literature, searching PubMed for articles on this rare tumor entity, with a focus on tumor biology, advanced neurosurgical opportunities for safe tumor resection, and multimodal treatment options. Adult medulloblastoma occurs at a rate of 0.6 per one million people per year. There is a slight disparity between male and female patients, and patients with a fair skin tone are more likely to have a medulloblastoma. Patients present with cerebellar signs and signs of elevated intracranial pressure. Diagnostic efforts should consist of cerebral MRI and MRI of the spinal axis. Cerebrospinal fluid should be investigated to look for tumor dissemination. Medulloblastoma tumors can be classified as classic, desmoplastic, anaplastic, and large cell, according to the WHO tumor classification. Molecular subgroups include WNT, SHH, group 3, and group 4 tumors. Further molecular analyses suggest that there are several subgroups within the four existing subgroups, with significant differences in patient age, frequency of metastatic spread, and patient survival. As molecular markers have started to play an increasing role in determining treatment strategies and prognosis, their importance has increased rapidly. Treatment options include microsurgical tumor resection and radiotherapy and, in addition, chemotherapy that respects the tumor biology of individual patients offers targeted therapeutic approaches. For neurosurgeons, intraoperative imaging and tumor fluorescence may improve resection rates. Disseminated disease, residual tumor after surgery, lower radiation dose, and low Karnofsky performance status are all suggestive of a poor outcome. Extraneural spread occurs only in very few cases. The reported 5-year-survival rates range between 60% and 80% for all adult medulloblastoma patients.