Computational fluid dynamics; a new diagnostic tool in giant intracerebral aneurysm treatment.

Giant intracerebral aneurysms (GIA) comprise up to 5 % of all intracranial aneurysms. The indirect surgical strategy, which leaves the GIA untouched but reverses the blood flow by performing a bypass in combination with proximal parent artery occlusion is a useful method to achieve spontaneous aneurysm occlusion. The goal of this study was to assess the utility of computational fluid dynamics (CFD) in preoperative GIA treatment planning. We hypothesise that CFD simulations will predict treatment results. A fluid-structure interaction (FSI) CFD investigation was performed for the entire arterial brain circulation. The analyses were performed in three patient-specific CT angiogram models. The first served as the reference geometry with a C6 internal carotid artery (ICA) GIA, the second a proximal parent artery occlusion (PAO) and virtual bypass to the frontal M2 branch of the middle cerebral artery (MCA), and the third a proximal PAO in combination with a temporal M2 branch bypass. The volume of "old blood", flow residence time (FRT), dynamic viscosity and haemodynamic changes were also analysed. The "old blood" within the aneurysm in the bypass models reached 41 % after 20 cardiac cycles while in the reference model it was fully washed out. In Bypass 2 "old blood" was also observed in the main trunk of the MCA after 20 cardiac cycles. Extrapolation of the results yielded a duration of 4 years required to replace the "old blood" inside the aneurysm after bypass revascularization. In both bypass models a 7-fold increase in mean blood viscosity in the aneurysm region was noted. Bypass revascularization combined with proximal PAO favours thrombosis. Areas prone to thrombus formation, and subsequently the treatment outcomes, were accurately identified in the preoperative model. Virtual surgical operations can give a remarkable insight into haemodynamics that could support operative decision-making.

Intracranial bypass for giant aneurysms treatment assessed by computational fluid dynamics (CFD) analysis.

Unruptured giant intracranial aneurysms (GIA) are those with diameters of 25 mm or greater. As aneurysm size is correlated with rupture risk, GIA natural history is poor. Parent artery occlusion or trapping plus bypass revascularization should be considered to encourage intra-aneurysmal thrombosis when other treatment options are contraindicated. The mechanistic background of these methods is poorly studied. Thus, we assessed the potential of computational fluid dynamics (CFD) and fluid-structure interaction (FSI) analyses for clinical use in the preoperative stage. A CFD investigation in three patient-specific flexible models of whole arterial brain circulation was performed. A C6 ICA segment GIA model was created based on CT angiography. Two models were then constructed that simulated a virtual bypass in combination with proximal GIA occlusion, but with differing middle cerebral artery (MCA) recipient vessels for the anastomosis. FSI and CFD investigations were performed in three models to assess changes in flow pattern and haemodynamic parameters alternations (wall shear stress (WSS), oscillatory shear index (OSI), maximal time averaged WSS (TAWSS), and pressure). General flow splitting across the entire domain was affected by virtual bypass procedures, and any deficiency was partially compensated by a specific configuration of the circle of Willis. Following the implementation of bypass procedures, a reduction in haemodynamic parameters was observed within the aneurysm in both cases under analysis. In the case of the temporal MCA branch bypass, the decreases in the studied parameters were slightly greater than in the frontal MCA branch bypass. The reduction in the magnitude of the chosen area-averaged parameters (averaged over the aneurysm wall surface) was as follows: WSS 35.7%, OSI 19.0%, TAWSS 94.7%, and pressure 24.2%. FSI CFD investigation based on patient-specific anatomy models with subsequent stimulation of virtual proximal aneurysm occlusion in conjunction with bypass showed that this method creates a pro-thrombotic favourable environment whilst reducing intra-aneurysmal pressure leading to shrinking. MCA branch recipient selection for optimum haemodynamic conditions should be evaluated individually in the preoperative stage.

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options. Objective: To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH. Design, Setting, and Participants: This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated. Intervention: During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group). Main Outcome and Measures: The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography. Results: Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups. Conclusions and Relevance: These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04269408.

Imaging meningioma biology: Machine learning predicts integrated risk score in WHO grade 2/3 meningioma.

Background: Meningiomas are the most common primary brain tumors. While most are benign (WHO grade 1) and have a favorable prognosis, up to one-fourth are classified as higher-grade, falling into WHO grade 2 or 3 categories. Recently, an integrated risk score (IRS) pertaining to tumor biology was developed and its prognostic relevance was validated in a large, multicenter study. We hypothesized imaging data to be reflective of the IRS. Thus, we assessed the potential of a machine learning classifier for its noninvasive prediction using preoperative magnetic resonance imaging (MRI). Methods: In total, 160 WHO grade 2 and 3 meningioma patients from 2 university centers were included in this study. All patients underwent surgery with histopathological workup including methylation analysis. Preoperative MRI scans were automatically segmented, and radiomic parameters were extracted. Using a random forest classifier, 3 machine learning classifiers (1 multiclass classifier for IRS and 2 binary classifiers for low-risk and high-risk prediction, respectively) were developed in a training set (120 patients) and independently tested in a hold-out test set (40 patients). Results: Multiclass IRS classification had a test set area under the curve (AUC) of 0.7, mostly driven by the difficulties in clearly separating medium-risk from high-risk patients. Consequently, a classifier predicting low-risk IRS versus medium-/high-risk showed a very high test accuracy of 90% (AUC 0.88). In particular, "sphericity" was associated with low-risk IRS classification. Conclusion: The IRS, in particular molecular low-risk, can be predicted from imaging data with high accuracy, making this important prognostic classification accessible by imaging.

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

Determinants of cerebral radionecrosis in animal models: A systematic review.

BACKGROUND: Radionecrosis is a common complication in radiation oncology, while mechanisms and risk factors have yet to be fully explored. We therefore conducted a systematic review to understand the pathogenesis and identify factors that significantly affect the development. METHODS: We performed a systematic literature search based on the PRISMA guidelines using PubMed, Ovid, and Web of Science databases. The complete search strategy can be found as a preregistered protocol on PROSPERO (CRD42023361662). RESULTS: We included 83 studies, most involving healthy animals (n = 72, 86.75 %). High doses of hemispherical irradiation of 30 Gy in rats and 50 Gy in mice led repeatedly to radionecrosis among different studies and set-ups. Higher dose and larger irradiated volume were associated with earlier onset. Fractionated schedules showed limited effectiveness in the prevention of radionecrosis. Distinct anatomical brain structures respond to irradiation in various ways. White matter appears to be more vulnerable than gray matter. Younger age, more evolved animal species, and genetic background were also significant factors, whereas sex was irrelevant. Only 13.25 % of the studies were performed on primary brain tumor bearing animals, no studies on brain metastases are currently available. CONCLUSION: This systematic review identified various factors that significantly affect the induction of radionecrosis. The current state of research neglects the utilization of animal models of brain tumors, even though patients with brain malignancies constitute the largest group receiving brain irradiation. This latter aspect should be primarily addressed when developing an experimental radionecrosis model for translational implementation.

Bedside Technique for the Implantation of Licox Brain Tissue Oxygen Probes in Occipital Regions: A Technical Note.

BACKGROUND: Continuous bedside monitoring of brain tissue oxygen levels is a crucial component in the management of comatose patients suffering from acute brain injury on neurointensive care units. Ensuring sufficient brain oxygenation is recognized as an essential objective within neurocritical care, aimed at safeguarding patients from secondary ischemia. Hypoperfusion in occipital and the posterior watershed regions often remains undetected, as the placement of probes in these areas is challenging. A major concern is that patients would have to lie on the traditionally used implanted bolts due to the occipital entry point of the probes. Therefore, we present a novel technique compatible with magnetic resonance imaging that enables bedside placement of brain tissue oxygen probes without the use of a bolt in these areas. METHODS: We conducted bedside implantations of Licox brain tissue oxygenation probes through Frazier's point utilizing peripheral venous cannulas on burr holes eliminating the need for bolts. RESULTS: A novel approach was successfully established for the bedside implantation of a Licox brain tissue oxygenation probe for occipital regions. CONCLUSIONS: This technical note describes the feasibility of a novel, simple, and straightforward bedside technique for boltless implantation of Licox brain tissue oxygen probes leading to rigid fixation and compatibility with magnetic resonance imaging.

Conceptualisation and Implementation of a Competency-based Multidisciplinary Course for Medical Students in Neurosurgery.

The field of medicine is quickly evolving and becoming increasingly more multidisciplinary and technologically demanding. Medical education, however, does not yet adequately reflect these developments and new challenges, which calls for a reform in the way aspiring medical professionals are taught and prepared for the workplace. The present article presents an attempt to address this shortcoming in the form of a newly conceptualized course for medical students with a focus on the current demands and trends in modern neurosurgery. Competency-based education is introduced as a conceptual framework comprising academic and operational competence as well as life-world becoming. This framework provides a sound educational foundation for future medical professionals, equipping them with the knowledge as well as skills needed to successfully navigate the medical field in the current day and age. Three competencies are identified that are central to day-to-day medical practice, namely digitalization, multidisciplinarity, and the impact of recent developments on the changing patient-practitioner relationship. These competencies are relevant for all medical disciplines, but are demonstrated here in a neurosurgical context and visualized using a real patient's case study. Students follow this sample patient's way through each step of the neurosurgical workflow, from planning to performing the procedure, and can see for themselves the importance and application of the aforementioned competencies based on this real-world example. Courses such as the one presented here may prepare medical students more adequately for their future work by combining theoretical and practical skills and critical reflection, thereby providing holistic and practical insights as well as a conceptual framework for their future careers.

Influence of the sagittal spinal profile type on the long-term outcome of patients with symptomatic lumbar spinal stenosis after microsurgical decompression.

OBJECTIVE: Microsurgical decompression for patients with symptomatic lumbar spinal stenosis (LSS) has demonstrated long-term improvement concerning pain and function. Nonetheless, a considerable proportion of these patients do not experience satisfactory alleviation of symptoms. Previous studies have not found a direct influence of single sagittal parameters on patient outcomes. However, recent research indicates that a composite of parameters, presented in specific sagittal profile types (SPTs) that were defined by Roussouly and colleagues, may affect these outcomes. This study aims to investigate the impact of SPT on long-term outcomes of patients with LSS following microsurgical decompression. METHODS: This study is a prospective clinical observation. Patients with symptomatic LSS, who underwent microsurgical treatment and had long-term follow-up data for at least 36 months, were included. Patients with spinal deformity, fractures, or significant instability were excluded. Outcomes were measured using the numeric rating scale for pain, 36-Item Short Form Health Survey for quality of life, walking distance, Oswestry Disability Index, Roland-Morris Disability Questionnaire, and Odom's criteria. SPT was determined in blinded fashion by using preoperative long standing radiographs. RESULTS: The initial population of this observational study consisted of 128 patients, with long-term results available for 87 individuals, including 24 patients with SPT1, 20 with SPT2, 27 with SPT3, and 16 with SPT4. The average age was 70 years, with a slight male majority (56.3%) and a mean BMI of 27.9 kg/m2. After a median follow-up of 48 months, all groups showed significant improvement in walking distance, leg pain, and disability. Overall, 75% reported satisfaction with the surgery. However, patients with SPT1, which is characterized by low sacral slope and specific spinal curvatures, experienced significantly less improvement in back pain (p = 0.018) and related disability (p = 0.030), and lower satisfaction compared to other SPT groups (p = 0.008). CONCLUSIONS: The sagittal spinal type is influencing the long-term outcome of patients suffering from symptomatic LSS. Patients with a combination of a flat sacral slope and a low overall lumbar lordosis with a high lordosis in the lower lumbar spine (i.e., spinal SPT1) showed worse outcome concerning back pain and had decreased satisfaction with surgery than comparable subjects from other SPT groups. Consequently, the authors recommend the assessment of sagittal spinal types in patients diagnosed with symptomatic spinal stenosis prior to decompression surgery. Inclusion of SPT in the preoperative consultation process can provide valuable insights, potentially guiding practitioners to more tailored patient counseling.

Automated detection of early signs of irreversible ischemic change on CTA source images in patients with large vessel occlusion.

PURPOSE: To create and validate an automated pipeline for detection of early signs of irreversible ischemic change from admission CTA in patients with large vessel occlusion (LVO) stroke. METHODS: We retrospectively included 368 patients for training and 143 for external validation. All patients had anterior circulation LVO stroke, endovascular therapy with successful reperfusion, and follow-up diffusion-weighted imaging (DWI). We devised a pipeline to automatically segment Alberta Stroke Program Early CT Score (ASPECTS) regions and extracted their relative Hounsfield unit (rHU) values. We determined the optimal rHU cut points for prediction of final infarction in each ASPECT region, performed 10-fold cross-validation in the training set, and measured the performance via external validation in patients from another institute. We compared the model with an expert neuroradiologist for prediction of final infarct volume and poor functional outcome. RESULTS: We achieved a mean area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of 0.69±0.13, 0.69±0.09, 0.61±0.23, and 0.72±0.11 across all regions and folds in cross-validation. In the external validation cohort, we achieved a median [interquartile] AUC, accuracy, sensitivity, and specificity of 0.71 [0.68-0.72], 0.70 [0.68-0.73], 0.55 [0.50-0.63], and 0.74 [0.73-0.77], respectively. The rHU-based ASPECTS showed significant correlation with DWI-based ASPECTS (rS = 0.39, p<0.001) and final infarct volume (rS = -0.36, p<0.001). The AUC for predicting poor functional outcome was 0.66 (95%CI: 0.57-0.75). The predictive capabilities of rHU-based ASPECTS were not significantly different from the neuroradiologist's visual ASPECTS for either final infarct volume or functional outcome. CONCLUSIONS: Our study demonstrates the feasibility of an automated pipeline and predictive model based on relative HU attenuation of ASPECTS regions on baseline CTA and its non-inferior performance in predicting final infarction on post-stroke DWI compared to an expert human reader.

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas.

The combination of DNA methylation analysis with histopathological and genetic features allows for a more accurate risk stratification and classification of meningiomas. Nevertheless, the implications of this classification for patients with grade 2 meningiomas, a particularly heterogeneous tumor entity, are only partially understood. We correlate the outcomes of histopathologically confirmed grade 2 meningioma with an integrated molecular-morphologic risk stratification and determine its clinical implications. Grade 2 meningioma patients treated at our institution were re-classified using an integrated risk stratification involving DNA methylation array-based data, copy number assessment and TERT promoter mutation analyses. Grade 2 meningioma cases according to the WHO 2021 criteria treated between 2007 and 2021 (n = 100) were retrospectively analyzed. The median clinical and radiographic follow-up periods were 59.8 and 54.4 months. A total of 38 recurrences and 17 deaths were observed. The local control rates of the entire cohort after 2-, 4-, and 6-years were 84.3%, 68.5%, and 50.8%, with a median local control time of 77.2 months. The distribution of the integrated risk groups were as follows: 31 low, 54 intermediate, and 15 high risk cases. In the multivariable Cox regression analysis, integrated risk groups were significantly associated with the risk of local recurrence (hazard ratio (HR) intermediate: 9.91, HR high-risk: 7.29, p < 0.01). Gross total resections decreased the risk of local tumor progression (HR gross total resection: 0.19, p < 0.01). The comparison of 1p status and integrated risk groups (low vs. intermediate/high) revealed nearly identical local control rates within their respective subgroups. In summary, only around 50% of WHO 2021 grade 2 meningiomas have an intermediate risk profile. Integrated molecular risk stratification is crucial to guide the management of patients with grade 2 tumors and should be routinely applied to avoid over- and undertreatment, especially concerning the use of adjuvant radiotherapy.

A prognostic neural epigenetic signature in high-grade glioma.

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes.

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Association of Fluid Balance and Hemoglobin Decline With Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: To explore the relationship between fluid balance and hemoglobin decline with secondary infarctions and neurologic outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients. DESIGN: Secondary analysis of the Earlydrain trial, a prospective randomized controlled study investigating prophylactic lumbar drain use in aSAH patients. SETTING: Patients with aSAH treated in ICUs at 19 tertiary hospitals in Germany, Switzerland, and Canada. PATIENTS: From January 2011 to January 2016, 287 patients were enrolled in the Earlydrain trial. Only files with complete information on both daily hemoglobin and balance values were used, leaving 237 patients for analysis. INTERVENTIONS: Investigation of fluid balance management and hemoglobin levels during the initial 8 days post-aSAH to establish thresholds for unfavorable outcomes and assess their impact on secondary infarctions and 6-month neurologic outcome on the modified Rankin Scale (mRS). MEASUREMENTS AND MAIN RESULTS: Patients with unfavorable outcome after 6 months (mRS > 2) showed greater hemoglobin decline and increased cumulative fluid balance. A significant inverse relationship existed between fluid balance and hemoglobin decline. Thresholds for unfavorable outcome were 10.4 g/dL hemoglobin and 4894 mL cumulative fluid balance in the first 8 days. In multivariable analysis, fluid balance, but not fluid intake, remained significantly associated with unfavorable outcome, while the influence of hemoglobin lessened. Fluid balance but not hemoglobin related to secondary infarctions, with the effect being significant after inverse probability of treatment weighting. Transfusion was associated with unfavorable outcomes. CONCLUSIONS: Increased fluid balance influences hemoglobin decline through hemodilution. Fluid overload, rather than a slight decrease in hemoglobin levels, appears to be the primary factor contributing to poor outcomes in aSAH patients. The results suggest aiming for euvolemia and that a modest hemoglobin decline may be tolerated. It may be advisable to adopt a restrictive approach to transfusions, as they can potentially have a negative effect on outcome.

Low-frequency repetitive transcranial magnetic stimulation in patients with motor deficits after brain tumor resection: a randomized, double-blind, sham-controlled trial.

Objective: Surgical resection of motor eloquent tumors poses the risk of causing postoperative motor deficits which leads to reduced quality of life in these patients. Currently, rehabilitative procedures are limited with physical therapy being the main treatment option. This study investigated the efficacy of repetitive navigated transcranial magnetic stimulation (rTMS) for treatment of motor deficits after supratentorial tumor resection. Methods: This randomized, double-blind, sham-controlled trial (DRKS00010043) recruited patients with a postoperatively worsened upper extremity motor function immediately postoperatively. They were randomly assigned to receive rTMS (1Hz, 110% RMT, 15 minutes, 7 days) or sham stimulation to the motor cortex contralateral to the injury followed by physical therapy. Motor and neurological function as well as quality of life were assessed directly after the intervention, one month and three months postoperatively. Results: Thirty patients were recruited for this study. There was no significant difference between both groups in the primary outcome, the Fugl Meyer score three months postoperatively [Group difference (95%-CI): 5.05 (-16.0; 26.1); p=0.631]. Patients in the rTMS group presented with better hand motor function one month postoperatively. Additionally, a subgroup of patients with motor eloquent ischemia showed lower NIHSS scores at all timepoints. Conclusions: Low-frequency rTMS facilitated the recovery process in stimulated hand muscles, but with limited generalization to other functional deficits. Long-term motor deficits were not impacted by rTMS. Given the reduced life expectancy in these patients a shortened recovery duration of deficits can still be of high significance. Clinical Trial Registration: https://drks.de/DRKS00010043.

Preoperatively-determined Red Distribution Width (RDW) predicts prolonged length of stay after single-level spinal fusion in elderly patients.

Introduction: Elderly patients receiving lumbar fusion surgeries present with a higher risk profile, which necessitates a robust predictor of postoperative outcomes. The Red Distribution Width (RDW) is a preoperative routinely determined parameter that reflects the degree of heterogeneity of red blood cells. Thereby, RDW is associated with frailty in hospital-admitted patients. Research question: This study aims to elucidate the potential of RDW as a frailty biomarker predictive of prolonged hospital stays following elective mono-segmental fusion surgery in elderly patients. Material and methods: In this retrospective study, we included all patients with age over 75 years that were treated via lumbar single-level spinal fusion from 2015 to 2022 at our tertiary medical center. Prolonged length of stay (pLOS) was defined as a length ≥ the 3rd quartile of LOS of all included patients. Classical correlation analysis, Receiver-operating characteristic (ROC) and new machine learning algorithms) were used. Results: A total of 208 patients were included in the present study. The median age was 77 (IQR 75-80) years. The median LOS of the patients was 6 (IQR 5-8) days. The data shows a significant positive correlation between RDW and LOS. RDW is significantly enhanced in the pLOS group. New machine learning approaches with the imputation of multiple variables can enhance the performance to an AUC of 71%. Discussion and conclusion: RDW may serve as a predictor for a pLOS in elderly. These results are compelling because the determination of this frailty biomarker is routinely performed at hospital admission. An improved prognostication of LOS could enable healthcare systems to distribute constrained hospital resources efficiently, fostering evidence-based decision-making processes.

Sex-dependent characteristics and outcomes after clipping of unruptured intracranial aneurysms: a multicenter propensity score-matched study.

OBJECTIVE: Disparities in the epidemiology and growth rates of aneurysms between the sexes are known. However, little is known about sex-dependent outcomes after microsurgical clipping of unruptured intracranial aneurysms (UIAs). The aim of this study was to examine sex differences in characteristics and outcomes after microsurgical clipping of UIAs and to perform a propensity score-matched analysis using an international multicenter cohort. METHODS: This retrospective cohort study involved the participation of 15 centers spanning four continents. It included adult patients who underwent clipping of UIAs between January 2016 and December 2020. Patients were stratified according to their sex and analyzed for differences in morbidities and aneurysm characteristics. Based on this stratification, female patients were matched to male patients in a 1:1 ratio with a caliper width of 0.1 using propensity score matching. Endpoints included postoperative complications, neurological performance, and aneurysm occlusion at discharge and 24 months after clip placement. RESULTS: A total of 2245 patients with a mean age of 57.3 (range 20-87) years were included. Of these patients, 1675 (74.6%) were female. Female patients were significantly older (mean 57.6 vs 56.4 years, p = 0.03) but had fewer comorbidities. Aneurysms of the internal carotid artery (7.1% vs 4.2%), posterior communicating artery (6.9% vs 1.9%), and ophthalmic artery (6.0% vs 2.8%) were more commonly treated surgically in females, while clipping of aneurysms of the anterior communicating artery was more frequent in males (17.0% vs 25.3%; all p < 0.001). After propensity score matching, female patients were found to have had significantly fewer pulmonary complications (1.4% vs 4.2%, p = 0.01). However, general morbidity (24.5% vs 25.2%, p = 0.72) and mortality (0.5% vs 1.1%, p = 0.34), as well as neurological performance (p = 0.58), were comparable at discharge in both sexes. Lastly, rates of aneurysm occlusion at the time of discharge (95.5% vs 94.9%, p = 0.71) and 24 months after surgery (93.8% vs 96.1%, p = 0.22) did not significantly differ between male and female patients. CONCLUSIONS: Despite overall differences between male and female patients in demographics, comorbidities, and treated aneurysm location, sex did not relevantly affect surgical performance or perioperative complication rates.

Analysis of Cerebral Spinal Fluid Drainage and Intracranial Pressure Peaks in Patients with Subarachnoid Hemorrhage.

BACKGROUND: After aneurysmal subarachnoid hemorrhage (aSAH), elevated intracranial pressure (ICP) due to disrupted cerebrospinal fluid (CSF) dynamics is a critical concern. An external ventricular drainage (EVD) is commonly employed for management; however, optimal strategies remain debated. The randomized controlled Earlydrain trial showed that an additional prophylactic lumbar drainage (LD) after aneurysm treatment improves neurological outcome. We performed a post hoc investigation on the impact of drainage volumes and critical ICP values on patient outcomes after aSAH. METHODS: Using raw patient data from Earlydrain, we analyzed CSF drainage amounts and ICP measurements in the first 8 days after aSAH. Outcomes were the occurrence of secondary infarctions and the score on the modified Rankin scale after 6 months, dichotomized in values of 0-2 as favorable and 3-6 as unfavorable. Repeated measurements were considered with generalized estimation equations. RESULTS: Earlydrain recruited 287 patients, of whom 221 received an EVD and 140 received an LD. Higher EVD volumes showed a trend to more secondary infarctions (p = 0.09), whereas higher LD volumes were associated with less secondary infarctions (p = 0.009). The mean total CSF drainage was 1052 ± 659 mL and did not differ concerning infarction and neurological outcome. Maximum ICP values were higher in patients with poor outcomes but not related to drainage volumes via EVD. After adjustment for aSAH severity and total CSF drainage, higher LD volume was linked to favorable outcome (per 100 mL: odds ratio 0.61 (95% confidence interval 0.39-0.95), p = 0.03), whereas higher EVD amounts were associated with unfavorable outcome (per 100 mL: odds ratio 1.63 (95% confidence interval 1.05-2.54), p = 0.03). CONCLUSIONS: Findings indicate that effects of CSF drainage via EVD and LD differ. Higher amounts and higher proportions of LD volumes were associated with better outcomes, suggesting a potential quantity-dependent protective effect. Optimizing LD volume and mitigating ICP spikes may be a strategy to improve patient outcomes after aSAH. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01258257.