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Abstract BACKGROUND: For appropriate use of available intraoperative imaging techniques in glioblastoma (GB) surgery, it is crucial to know the potential of the respective techniques in tumor detection. OBJECTIVE: To assess histopathological basis of imaging results of intraoperative magnetic resonance imaging (iMRI), 5-aminolevulinic acid (5-ALA), and linear array intraoperative ultrasound (lioUS). METHODS: We prospectively compared the imaging findings of iMRI, 5-ALA, and lioUS at 99 intraoperative biopsy sites in 33 GB patients during resection control. Histological classification of specimens, tumor load, presence of necrosis, presence of vascular malformations, and O6-methylguanin-DNA methyltransferase (MGMT) promoter state was correlated with imaging findings. RESULTS: Solid tumor was found in 57%, infiltration zone in 42%, and no tumor in 1% of specimens. However, imaging was negative in iMRI in 49%, using 5-ALA in 17%, and in lioUS in 21%. In positive imaging results, share of solid tumor was highest in 5-ALA (65%) followed by lioUS (60%) and lowest in iMRI (55%). In comparison to 5-ALA, iMRI had a high share of solid tumor in specimens when showing intermediate results. Sensitivity for invasive tumor was higher in 5-ALA (84%) and lioUS (80%) than in iMRI (50%). We found a significant correlation of 5-ALA with classification of specimen, presence of necrosis, and microproliferations. Methylated MGMT promoter correlated with positive findings in 5-ALA. lioUS and iMRI showed no correlations with histopathological findings. CONCLUSION: All of the assessed established imaging techniques detect infiltrating tumor only to a certain extent. Only 5-ALA showed a significant correlation with histopathological findings. Interestingly, tumor remnants in an MGMT-methylated tumor are more likely to be visible using 5-ALA as in unmethylated tumors.

Background: Decompressive craniectomy (DC) is a life-saving intervention for refractory intracranial pressure (ICP). While outcomes in adults are well documented, pediatric data, especially concerning pupillomotor dysfunction, remain limited. Anisocoria is generally considered a marker of severe neurological compromise, but its clinical relevance in children undergoing DC has not been adequately studied. Methods: We retrospectively reviewed 25 pediatric patients treated with DC between 2004 and 2024. Demographic, radiological and clinical data included age, sex, hospital stay, operative time, etiology, side of craniectomy, preoperative midline (ML) shift, Marshall score, Rotterdam score, Glasgow Coma Scale (GCS) and pupillary status before surgery. Functional outcomes were assessed using the pediatric version of the Glasgow Outcome Scale Extended (pGOS-E) at discharge, after 3 months, 1, 2 and 4 years. Results: The majority of patients were school-aged children with a median age of 10 (range 0–17) years. Traumatic brain injury accounted for 16 cases and represented the leading etiology for DC. Pupillomotor dysfunction (anisocoria or bilateral fixed pupillary dilatation) was observed in 15 of 25 patients, 47% of whom died during hospitalization, demonstrating a significant association with in-hospital mortality (p = 0.02). However, survivors with primary pupillomotor dysfunction demonstrated a favorable recovery at 12 months with a median pGOS-E of 6 (range 4–8), indicating moderate disability. A preoperative ML-shift > 5 mm was not associated with lower pGOS-E scores during follow-up (p > 0.05). Bone flap autolysis was observed in 12 out of 14 children (86%) receiving autologous cranioplasty, and 8 (57%) patients required revision surgery with synthetic material. Conclusions: In pediatric patients, pupillomotor dysfunction is associated with higher early mortality but does not reliably exclude favorable long-term outcomes. Compared with adult cohorts, children appear to have a greater potential for neurological recovery, suggesting that severe initial clinical findings alone should not preclude timely surgical intervention.

Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy.

Peripheral nerve injuries remain challenging due to the limited regenerative capacity over long distances and the complexity of repair mechanisms. While autologous nerve grafts are the clinical gold standard, their use is restricted by donor-site morbidity and tissue availability. Tissue-engineered materials such as nerve guidance conduits (NGCs), hydrogels, and bioactive scaffolds offer alternative solutions by providing structural support and delivering trophic, immunomodulatory, or electrical cues. This mini-review categorizes these materials by their functional properties, including drug delivery, cell integration, and electroactivity, and critically assesses their preclinical performance and translational limitations. Natural materials such as collagen and chitosan exhibit good biocompatibility but limited mechanical stability and variability. Synthetic polymers and electroactive materials allow for customization and controlled stimulation but often provoke immune responses or degrade into harmful byproducts. Advanced drug-delivery systems using hydrogels and microspheres enable targeted factor release, yet reproducibility and kinetics remain critical barriers. Cell-integrated constructs, including Schwann cell-like cells and engineered neural tissue, offer high regenerative potential but face challenges in scalability, regulatory classification, and manufacturing. Importantly, many preclinical studies do not benchmark against autografts or address neuroma formation, fibrosis, and delayed regeneration—key issues in human lesions. A summary of preclinical constructs and translational barriers is provided to highlight recurring obstacles such as immune incompatibility, insufficient vascular integration, and regulatory hurdles. Future research must refine model systems, align regulatory strategies, and enhance construct functionality to enable effective clinical translation.

Objectives: Early death after trauma has been described several times. Little is known about it after traumatic brain injury (TBI) and decompressive craniectomy (DC). The aim of this study was to characterize patients who die after a TBI and DC during their in-hospital stay. Methods: In a subgroup analysis of a retrospective, multicenter, and observational study, non-survivors from in-hospital stays treated for severe TBI and DC were included. Propensity score matching (PSM) was used. Results: A total of 223 patients with severe TBI were treated with DC, and there were 65 (29.1%) patients who did not survive. Of these, 22 (33.8%) died within the first 24 h. Non-survivors were older (p = 0.010), and pupillomotor dysfunction and a higher heart rate on admission were more common (p < 0.001). PSM patients for overall survival (41, 18.4%) differed in mean heart rate from the deceased (p = 0.030). In a multivariate model, age (OR: 1.045, p = 0.013, CI95%: 1.010 to 1.082), Quick value (OR: 0.965, p = 0.049, CI95%: 0.931 to 1.000), and heart rate (OR: 1.099, p = 0.030, CI95%: 1.009 to 1.197) were confirmed as predictive factors. Conclusions: Even after DC, known factors, such as chronological age and comorbidities, have a significant influence on mortality. The value of DC in an aging society for a particular severity of TBI should be further assessed on the basis of prospective studies.

Nerve tumors in the retroperitoneal space are a rarity. Radical surgery according to soft tissue tumors can lead to persistent pain and neurological deficits. This study aims to evaluate clinical outcomes of patients treated by a visceral- / neurosurgical approach. 33 patients with a retroperitoneal nerve tumor underwent surgery between 01/2002 and 12/2022 at our department. A visceral surgeon provided access to the retroperitoneal space, followed by micro-neurosurgical tumor preparation under neuromonitoring. Clinical examination and MRI were performed 12 weeks after surgery and further 3 months (WHO grade > 1) or 12 months (WHO grade 1). Further examinations were based on MRI findings and residual symptoms with median follow-up time of 24 months. One patient was treated for two distinct masses resulting in a total of 34 histological findings. Schwannomas ( n  = 15; 44.1%) and neurofibromas ( n  = 10; 29.4%) were the most common tumors. Long-term improvements were noted in radicular pain (15/18 patients; 83.3%), motor deficits (7/16 patients; 43.8%), abdominal discomfort and pain (5/7 patients; 71.4%). Recurrences were observed in 3/33 (9,1%) patients. This study represents the largest series of retroperitoneal BPNSTs treated with microsurgical techniques. Prospective multicenter studies are warranted to establish standardized treatment guidelines.

Background Glioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.

Objective In 2021, Rossi et al. developed a cortical mapping algorithm that enabled a reliable mapping of an anatomical subdivision of the precentral gyrus. This approach allowed for the differentiation between an anterior subregion, characterized by lower excitability and slower motor responses, and a posterior subregion (named “M1 proper”), exhibiting higher excitability and faster motor responses. Based on these findings, we conducted a navigated transcranial magnetic stimulation (nTMS) study to investigate whether this anatomical subdivision can also be identified using a non‐invasive mapping technique. Methods Fifteen healthy volunteers were examined. Using nTMS, the motor cortex at the hand knob area was subdivided into four distinct strips aligned parallel to the central sulcus: s, precentral non‐proper, precentral proper, and postcentral. After determining the resting motor threshold (RMT), 10 stimulation points in each strip were stimulated with 150% RMT. Electromyographic (EMG) amplitudes and latencies were recorded and compared across the four stimulation strips to detect potential differences. Results Although descriptively higher mean EMG amplitudes were observed in the precentral proper strip, generalized linear mixed‐effects modeling revealed no statistically significant differences in EMG amplitude between the precentral proper and non‐proper regions, nor across any of the four stimulation strips. Conclusions Using the applied protocol, a clear delineation between a functionally separated ventral and dorsal subdivision of the precentral gyrus could not be observed. However, it is noteworthy that the application of relatively high stimulation intensity may have masked subtle differences. Further examinations at the lower end of the stimulation spectrum (e.g., 90% or 100% RMT) or a specific paired pulse protocol may allow for a more precise differentiation between these two anatomical areas. Using navigated TMS, we investigated whether functional subdivisions of the primary motor cortex can be identified non‐invasively. No significant differences in excitability or latency were found between precentral subregions, suggesting that standard stimulation protocols may not reliably differentiate M1 proper from adjacent areas.

Background Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear. Methods PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4–5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0–4) and unfavorable (mRS 5–6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC. Discussion This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients. Trial registration DRKS DRKS00017650. Registered on 09 June 2019.

Objective: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). Methods: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV–V) and unfavourable outcome (GOS I to III). Results: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). Conclusion: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.