IntroductionThis retrospective, single-center study aimed to identify predictive factors for progression in postoperative residual findings of non-functioning pituitary macroadenomas (NFPMAs). The findings are intended to support individualized decisions regarding follow-up and adjuvant therapy.MethodsA retrospective analysis was conducted on 212 patients treated at a tertiary referral center between 2007 and 2023. Patients underwent MRI-guided, transnasal transsphenoidal surgery for histologically confirmed NFPMAs. Pre- and postoperative tumor volumes were assessed alongside demographic, clinical, and histopathological data. Tumor configuration was classified using Hardy and Knosp scales. Subgroups were defined based on postoperative imaging: stable residuals, progressive residuals, or recurrence after gross total resection (GTR). Statistical analyses included multivariate testing and ROC analysis to determine predictive cutoff values.ResultsOf the 212 patients, initial radiological gross total resection (GTR) was achieved in 94/212 (44.3%); during follow-up, 62/212 (29.2%) had durable complete resection without recurrence, while 32/212 (15.1%) developed recurrence after initial GTR. Among patients with residual findings, 76 (64.4%) exhibited stable tumors after a mean of follow-up of 39 months, while 42 (35.6%) showed progression, which correlated significantly with larger preoperative tumor volumes (median: 11.6 cm3 vs. 5.81 cm3, p < 0.001). ROC analysis identified 7.12 cm3 as the optimal cutoff for distinguishing stable from progressive residual tumor volumes (AUC = 0.748). No significant differences between stable and progressive groups were observed in Hardy or Knosp classifications. Postoperative cortisol levels were nominally higher in patients with progressive residuals (14.10 μg/dL vs. 10.83 μg/dL; p = 0.022; exploratory).ConclusionAccording to our study, preoperative and postoperative tumor volumes represent pragmatic prognostic markers of progression in NFPMAs, with a critical cutoff of 7.12 cm3 for stability. These findings could inform tailored follow-up strategies. Prospective studies are warranted to validate these results and further explore the impact of surgical and tumor characteristics on long-term outcomes.
Traumatic atlanto-occipital dislocation (AOD) is a rare, severe high-energy injury historically associated with near-100
Precise molecular characterization of glioblastoma (GB) is fundamental for accurate risk stratification and therapeutic planning. DNA methylation profiling reliably identifies key molecular features, including O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and specific molecular subtypes, such as receptor tyrosine kinase (RTK) I and II, and the mesenchymal (MES) subtype. In this study, we investigated the hypothesized correlation between these molecular profiles and preferential tumor locations, which could reveal a link to underlying tumor biology. We analyzed 227 GB patients characterized by DNA methylation profiling. To map significant clusters of tumor occurrence across subtypes and subcomponents, we performed voxel-wise analysis of differential involvement, utilizing 500 permutations to correct for multiple comparisons. While uncorrected frequency differential maps suggested localization tendencies for the RTK I, RTK II, and MES subtypes, stringent statistical correction revealed only one robust association: the non-enhancing component of MES tumors showed significant clustering in the left frontal lobe, the insula, and the temporal lobe. Contrary to prior literature, we observed no significant hemispheric preference regarding MGMT promoter methylation status. Our findings challenge prior assumptions regarding the spatial distinctiveness of GB subtypes and highlight the need to further elucidate the mechanisms governing tumorigenesis and spatial growth patterns.
Purpose Meningiomas (MNGs) occur in different histopathological subtypes. The WHO grading system classifies a subset as grade 2 and 3, indicating a more aggressive course. Recent advances in risk stratification introduces an integrated molecular-morphological score (IntS), offering improved risk prediction over the traditional WHO classification. This study aims to evaluate the prognostic utility of IntS in the context of the timing of adjuvant radiotherapy (RT). Methods This retrospective study analyzed 55 patients with histologically diagnosed WHO grade 2 and 3 MNG treated with adjuvant RT. Molecular analyses using Illumina 450k Human BeadChip and Illumina 850k EPIC stratified patients into 3 risk groups (low, intermediate and high) using an integrated model that combines WHO grading, Copy Number Variations (CNVs), and Methylation Families (MF). Results After 5 years a local failure-free survival (LFFS) rate of 0% in MF-malignant MNG contrasts with a LFFS rate of 77% and 58% in MF-benign and MF-intermediate MNG. A significant correlation between CNVs and LFFS was also observed in the adjuvant setting. The IntS model revealed distinct 5-year LFFS disparities across different risk categories, underscoring the impact of combined morphological and molecular characteristics on outcome. Conclusion The integration of DNA-methylation and CNV-profiles into the IntS unified risk score offer an enhanced prognostic differentiation of MNG patients. This approach shows a promising direction for guiding the optimal timing of adjuvant RT, offering a path toward more tailored treatment strategies for meningiomas.
Purpose This study compared laminectomy and hemilaminectomy for resection of spinal (sHBs), evaluating extent of resection, 12-month postoperative functional outcomes, perioperative complications overall, with particular attention to postoperative bleeding. Material and methods This retrospective international multicenter study included 280 primary sHB patients from 13 neuro-oncological centers who underwent either laminectomy (n = 125) or hemilaminectomy (n = 155). The endpoints were the extent of resection, functional outcomes at 12 months, and postoperative bleeding requiring retreatment. Multivariable logistic regression analysis was performed to determine independent risk factors associated with these outcomes. Results The rate of complete resection was similar between both surgical approaches, with 86.4% in the laminectomy group and 90.3% in the hemilaminectomy group (p = 0.35). Independent predictors of incomplete resection included preoperative modified McCormick >2 (OR: 4.29, p = 0.001), combined intra- and extramedullary tumor location (OR: 2.91, p = 0.03), and cervical or thoracic tumor location (OR: 3.38, p = 0.01). Functional outcomes at 12 months did not differ significantly between the laminectomy- and hemilaminectomy-groups (p = 0.97). Postoperative bleeding was more frequently observed in tumors involving two or more spinal segments (OR: 14.6, p = 0.01). The choice of surgical approach did not impact the incidence of postoperative bleeding (p = 0.55). Conclusion Laminectomy and hemilaminectomy result in comparable outcomes of sHB. Tumors affecting multiple spinal segments are associated with an increased risk of postoperative bleeding, while combined intra- and extramedullary growth, impaired preoperative functioning and non-lumbar location were associated with incomplete resection. Given the comparable outcomes, the selection of the surgical approach may be guided by surgeon preference and individual patient anatomy.
BACKGROUND:Evidence regarding the clinical course of unruptured giant intracranial aneurysms (GIAs) after conservative management (CON), microsurgical treatment (SURG) or endovascular treatment (EVT) remains limited. We aimed to assess mortality, functional outcome, symptom course and retreatment rates after different management strategies. METHODS:In this prospective, multinational registry, patients with unruptured GIAs treated at 37 neurovascular centres between 2008 and 2018 were included. Outcomes after CON, EVT or SURG were analysed with standardised 3-year follow-up. The study is registered at ClinicalTrials.gov. RESULTS:We included 339 patients of whom 22.7% received CON, 42.8% EVT and 34.5% SURG. Three-year survival was 64.0% (95% CI 53.73% to 76.20%) in the CON group, 82.0% (95% CI 75.42% to 89.17%) in the EVT group and 93.5% (95% CI 88.91% to 98.28%) in the SURG group (p<0.001). Favourable neurological outcome (modified Rankin Scale 0-2) declined to 53.0%, 66.9% and 75.7% in the CON, EVT and SURG groups, respectively (p<0.01). Symptom improvement at 3 years occurred in 10.3% of CON, 22.1% of EVT and 11.1% of SURG patients, while deterioration was observed in 7.7%, 8.5% and 15.8%, respectively. Retreatment was required in 22.8% of EVT patients and 6.2% of SURG patients (p<0.01). CONCLUSIONS:EVT and SURG were associated with significantly improved survival and functional outcomes compared with conservative management of unruptured GIAs. In patients eligible for intervention, both treatment modalities represent reasonable and effective options, with a high proportion of patients achieving favourable clinical outcomes. TRIAL REGISTRATION NUMBER:NCT02066493.
Cognitive impairments are common among patients suffering from brain tumors. Up to date, however, it is rarely assessed in clinical routine. This study aimed to evaluate pre- and postoperative neurocognitive performance in a wide range of patients suffering from gliomas representing clinical routine by using a test battery of easy-to-use and established neurocognitive tests. Patients undergoing microsurgical glioma resection between 04/2019 and 03/2021 were prospectively included. A structured test set for neurocognitive function was performed preoperatively in 33 patients and during follow-up in 14 patients. Data were converted into z-scores and combined with the corresponding cognitive domains. Thirty-three patients aged 49.2 ± 14.4 (22-81) years were included. The individual tests showed impairments preoperatively most frequently in the trail-making test B (TMT-B) in 63.6% of patients, followed by the Montreal Cognitive Assessment (MoCA) with 39.4%. Preoperatively, a clinically significant impairment was found in the domain of executive function and attention, with a mean domain score of -2.49. At follow-up, the group domain scores were impaired on the same cognitive domains as preoperatively, with executive function and attention significantly impaired (z = -2.58). Neurocognitive deficits are present in the majority of patients with glioma before surgery while still performing well in conventional scores regarding functional status. We did not observe any significant surgery-related deterioration in cognitive performance; however, this finding is compromised by a considerable number of patients lost to follow-up.
OBJECTIVES:To validate whether cerebrospinal fluid oxyhaemoglobin (CSF-Hb), measured from external ventricular or lumbar drains, is associated with secondary brain injury (SAH-SBI) after aneurysmal subarachnoid haemorrhage (aSAH) and to assess its value as a real-time monitoring biomarker. DESIGN:Pre-registered multicentre prospective observational cohort study. SETTING:Eight neurosurgical tertiary centres in Switzerland, Germany and Austria between August 2021 and June 2024. PARTICIPANTS:366 patients with aSAH (mean age 58 years; 65% women). Of these, 260 provided cerebrospinal fluid (CSF) samples via external ventricular drain (EVD; 2467 samples, median 10 days per patient) and 66 via lumbar drain (LD; 379 samples, median 6 days). INTERVENTIONS:Daily CSF samples were collected via EVD or LD from day 1 to day 14 after haemorrhage; no therapeutic interventions were tested. MAIN OUTCOME MEASURES:CSF-Hb and its metabolites were analysed post hoc in a blinded manner. The primary outcome was SAH-SBI, defined as a composite of angiographic vasospasm (aVSP), delayed cerebral ischaemia (DCI) and delayed ischaemic neurological deficits (DIND), assessed daily over 14 days. Secondary outcomes included temporal CSF-Hb profiles and associations with aneurysm location, haematoma volume, intraventricular haemorrhage, chronic hydrocephalus and 3 month functional outcome. RESULTS:CSF-Hb showed a delayed peak pattern: concentrations were low after aSAH, rose to a maximum on day 10 (EVD-derived CSF-Hb median 11.3 µM, IQR 2.64 to 25.90) and then declined. Larger haematoma volume (p<0.001) and intraventricular haemorrhage (p<0.001) were associated with higher EVD-derived CSF-Hb. SAH-SBI occurred in 209/366 patients (57%). Daily EVD-derived CSF-Hb showed no association with SAH-SBI (p=0.25) and only poor prognostic potential for same-day SAH-SBI (area under the curve 0.59, 95% CI 0.56 to 0.63), with substantial between-centre heterogeneity. In a post-hoc exploratory analysis, higher CSF methaemoglobin showed a positive point-estimate of association with SAH-SBI (OR 1.18 per log(µM), 95% CI 1.02 to 1.36). Higher acute-phase EVD-derived CSF-Hb was associated with chronic hydrocephalus and a poor 3 month functional outcome. Catheter-related infection rates were low (2.2%). CONCLUSIONS:In this preregistered multicentre validation study, EVD-derived CSF-Hb did not perform as a robust real-time monitoring biomarker for SAH-SBI, showing limited same-day discrimination and substantial between-centre heterogeneity. These findings argue against clinical implementation of CSF-Hb point-measurement as a single-parameter biomarker. Higher CSF methaemoglobin was associated with SAH-SBI; this hypothesis-generating observation requires prospective confirmation and motivates continued investigation of haemolysis-related pathways. Future work using the HeMoVal biobank will apply multi-marker, pathway-level analyses to define haemolysis-related biomarker signatures and provide a platform for robust external validation of future candidates. TRIAL REGISTRATION NUMBER:NCT04998370.
BACKGROUND/OBJECTIVE:Shunt-dependent hydrocephalus represents a major complication of aneurysmal subarachnoid hemorrhage (aSAH), yet no universally adopted CT-based prediction tool exists. Fisher-based scales suffer from a ceiling effect limiting discriminative capacity. Whether quantitative scores offer superior performance and whether blood compartments contribute differentially to shunt dependency remains unknown. METHODS:Retrospective single-center study of 285 consecutive aSAH patients (January 2020-December 2025). 6 scores assessed on admission CT: Fisher, Modified Fisher, Hijdra Cisternal, Hijdra Ventricular, Hijdra Total, and Modified Hijdra Total. Primary outcome was VP shunt dependency. Discriminative performance assessed using ROC analysis; pairwise comparisons via DeLong's method. RESULTS:Hijdra Total achieved highest AUC (0.763, 95% CI: 0.706-0.818), followed by Hijdra Cisternal (0.736), Modified Hijdra Total (0.733), and Hijdra Ventricular (0.725). All Hijdra-based scores outperformed Fisher (0.625) and Modified Fisher (0.648) (all P < 0.001). No significant difference between Hijdra Total and Modified Hijdra Total (P = 0.094), or between ventricular and cisternal subscores (P = 0.762). At optimal Hijdra, total cutoff ≥32: sensitivity 71%, specificity 73%, PPV 67%, NPV 76%. CONCLUSIONS:Hijdra Total outperforms Fisher-based scales for VP shunt prediction. No significant difference was observed between cisternal and ventricular blood compartments in predicting shunt dependency, consistent with the hypothesis that total blood burden rather than anatomical distribution drives hydrocephalus risk. This contrasts with vasospasm where ventricular exclusion improves performance, supporting compartment-specific score selection by clinical endpoint.
In 2022, a nationwide survey revealed heterogeneity and limited standardization in the implementation of molecular tumor boards (MTBs) for neuro-oncology in Germany. This follow-up study aimed to assess recent developments, structural changes, and the integration of digital tools. An anonymous online questionnaire was distributed to approximately 445 members of the German Neuro-Oncology Working Group (NOA). Items focused on MTB availability, frequency, tumor inclusion, recommendation pathways, implementation, digital infrastructure, and perceived barriers. 35 responses were collected. Respondents were primarily experienced neurosurgeons and neurologists working in certified university centers. Most were based in Bavaria, Baden-Württemberg, North Rhine–Westphalia, and Berlin. The number of in-house MTBs increased, with most boards meeting weekly. A broader range of tumor entities—including lower-grade gliomas—and earlier therapy lines are increasingly discussed. Recommendations were issued in fewer than half of cases, and over 30
Background:Evidence on the influence of eloquent brain areas on the effectiveness and side effects of radio-therapy (RT) remains limited. This study evaluated the relationship between eloquent brain regions, radiation dose, and tumor recurrence patterns in glioma patients. Methods:Preoperative navigated transcranial magnetic stimulation (nTMS) mapping of language and motor function, complemented by nTMS-based tractography, was performed. Magnetic resonance imaging of tumor recurrence was co-registered with RT treatment plans and functional nTMS data. Tumor growth direction, radiation dose to eloquent structures, and clinical outcomes were analyzed. Results:Seventy-two patients with glioblastoma, aged 57.7 ± 14.8 years, were included. Tumor recurrence toward eloquent brain areas, assessed either by volumetric or linear measurements, indicated growth affecting motor function in 68.1% and language function in 79.3% of patients. Following RT, new motor deficits occurred in 3/48 patients (6.3%) and language deterioration in 3/20 (15.0%). The mean dose to the corticospinal tract was 10.1 Gy in patients with motor decline versus 3.7 Gy in those without (P = .137). For language fiber tracts, corresponding doses were 34.1 Gy and 15.1 Gy (P = .073). Conclusions:Tumor recurrence toward eloquent brain areas was observed, with high radiation doses to eloquent brain areas being associated with higher rates of neurological deterioration. These findings create an ambiguous situation regarding the application of high radiation doses to the resection cavity facing eloquent brain areas while simultaneously ensuring optimal dose gradients to spare those.
Abstract Implantable brain-computer interfaces (iBCIs) with single-neuron resolution are showing great promise for restoring mobility and communication in individuals with spinal cord injury or motor neuron disease. Stroke is the most common cause of acquired brain injury and a major contributor to long-term disability, making chronic stroke a highly relevant indication for iBCIs. However, whether stable intracortical recordings can be obtained from the structurally lesioned human brain is unknown. We report recordings from four 64-channel microelectrode arrays implanted in a participant with chronic aphasia after a large left-hemispheric stroke. The arrays targeted right-hemispheric frontoparietal regions homotopic to the damaged left-hemispheric language network. Across 111 sessions spanning 1,240 days, unit yield and signal quality remained stable. Waveform-based tracking reliably identified individual units across sessions, including across extended recording gaps. Short- and long-term unit stability was comparable to previous reports from iBCI participants without structural brain lesions, and tracked units showed consistent spiking properties across sessions. Our findings provide the first evidence that single-neuron recordings can remain stable over the long term in the stroke-lesioned human brain. They establish the feasibility of chronic, cellular-resolution iBCIs after stroke and support the development of neurorestorative applications for deficits caused by structural brain injury.
Introduction Adult tethered cord syndrome (TCS) represents a heterogeneous group of congenital and acquired conditions. While primary untethering is an established treatment, re-untethering remains controversial because of concerns regarding limited neurological benefit and increased complication rates. Research question This study evaluates neurological outcomes after adults re-untethering surgery and identifies perioperative factors associated with clinical improvement. Methods We performed a retrospective single-center cohort analysis of all patients surgically treated for TCS between 2008 and 2024. Patients were dichotomized into primary untethering and secondary re-untethering groups. Neurological status was assessed using the McCormick grade. Neurological improvement was defined as improvement of ≥1 McCormick grade. Postoperative complications and revision surgeries were recorded. Age and affected spinal level were analyzed as potential modifiers of outcome. Results Seventy-one patients were included (median age 51.5 years); 42 underwent primary untethering and 29 re-untethering. Patients undergoing re-untethering presented with significantly worse baseline neurological status. Neurological improvement at discharge was more frequent after primary untethering (52.4% vs. 31.0%), but this difference reversed at follow-up, with higher improvement rates after secondary re-untethering (68.4% vs. 61.5%). Neither age nor affected spinal level significantly influenced neurological outcome or revision rates. Re-untethering was associated with more complex surgeries, and higher wound-healing complication rates. Discussion and Conclusion Despite worse baseline neurological status, re-untethering is not associated with inferior neurological outcomes compared with primary untethering. Neurological improvement appears to be a time-dependent process, and baseline impairment alone should not preclude surgical intervention. Re-untethering in adult patients should therefore be considered on an individual basis.
Despite advancements in bionic technology, disrupted afferent and efferent pathways in individuals with limb loss may hinder prosthetic embodiment. Transcranial Magnetic Stimulation (TMS) has emerged as a promising tool for investigating and modulating sensorimotor processes, though its application in neurorehabilitation for individuals with limb differences remains limited. This pilot study explores whether TMS over parietal regions associated with the grasping-function and motor planning can enhance the sense of embodiment and influence motor behaviour. In this feasibility protocol, six healthy participants and two prosthesis users underwent a virtual reality TMS-training protocol. Its effects were assessed through pre- and post-training evaluations using standard self-reported embodiment surveys, functional performance metrics, and a Locus of Attention Index. Participants completed two assessments without TMS, before and after a training session with TMS. Additionally, one final assessment with TMS was conducted, designed to evaluate its direct impact on performance metrics. Results in healthy participants indicate that while TMS did not significantly alter the perceived embodiment, it affected the visual attention allocation. Additionally, trajectory velocity differed between no-TMS and TMS assessments. Finally, the online system evaluation on two prosthesis users highlights the feasibility of applying parietal TMS in training for prosthetic embodiment research, warranting further investigation with larger and more comprehensive samples to better establish the role of TMS in sensorimotor rehabilitation with amputees.