Background: Primary central nervous system lymphoma (PCNSL) is a rare lymphoma of the central nervous system, usually of diffuse large B cell phenotype. Stereotactic biopsy followed by histopathology is the diagnostic standard. However, limited material is available from CNS biopsies, thus impeding an in-depth characterization of PCNSL. Methods: We performed flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing of PCNSL cells released from biopsy material, blood, and cerebrospinal fluid (CSF), and spatial transcriptomics of biopsy samples. Results: PCNSL-released cells were predominantly activated CD19⁺CD20⁺CD38⁺CD27⁺ B cells. In single-cell RNA sequencing, PCNSL cells were transcriptionally heterogeneous, forming multiple malignant B cell clusters. Hyperexpanded B cell clones were shared between biopsy- and CSF- but not blood-derived cells. T cells in the tumor microenvironment upregulated immune checkpoint molecules, thereby recognizing immune evasion signals from PCNSL cells. Spatial transcriptomics revealed heterogeneous spatial organization of malignant B cell clusters, mirroring their transcriptional heterogeneity across patients, and pronounced expression of T cell exhaustion markers, co-localizing with a highly malignant B cell cluster. Conclusions: Malignant B cells in PCNSL show transcriptional and spatial intratumor heterogeneity. T cell exhaustion is frequent in the PCNSL microenvironment, co-localizes with malignant cells, and highlights the potential of personalized treatments.

OBJECTIVE: Decompressive craniectomies (DCs) are performed on patients suffering large cerebral infarctions. The efficacy of this procedure has been demonstrated in several trials. In some cases, however, this procedure alone is not sufficient and patients still suffer refractory elevations of intracranial pressure (ICP). The goal of this study was to determine whether resection of infarcted tissue, termed strokectomy, performed as a second-look procedure after DC, improves outcome in selected cases.METHODS: The authors retrospectively evaluated data of patients who underwent a DC due to a cerebral infarction at their institution from 2009 to 2016, including patients who underwent a strokectomy procedure after DC. Clinical records, imaging data, outcome scores, and neurological symptoms were analyzed, and clinical outcomes and mortality rates in the strokectomy group were compared to those for similar patients in recently published randomized controlled trials.RESULTS: Of 198 patients who underwent DC due to cerebral infarction, 12 patients underwent strokectomy as a second surgical procedure, with a median National Institutes of Health Stroke Scale (NIHSS) score of 19 for patients with versus 16 for those without secondary strokectomy (p = 0.029). Either refractory increases of ICP > 20 mm Hg or dilated pupils in addition to herniation visible on CT images were triggers for strokectomy surgery. Ten of 12 (83%) patients had infarctions in more than one territory (p < 0.001). After 12 months, 43% of patients had a good outcome according to the modified Rankin Scale (mRS) score (≤ 3). In the subgroup of patients suffering infarctions in more than one vascular territory, functional outcome after 12 months was better (mRS ≤ 3 in 40% of patients in comparison to 9%; p = 0.027). A 1:3 case-control analysis matched to age, side of infarction, sex, and vascular territory confirmed these results (mRS ≤ 3, 42% in comparison to 11%; p = 0.032). Age, NIHSS score on admission, and number of vascular territories involved were identified as risk factors in multivariate analysis (p < 0.05). Patients in the strokectomy group had more infections (p < 0.001). According to these results, the authors developed a scale (Münster Stroke Score, 0–6 points) to predict whether patients might benefit from additional strokectomy. Receiver-operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.86 (p < 0.001). The authors recommend a Münster Stroke Score of ≥ 3 as a cutoff, with a sensitivity of 92% and specificity of 66%, for predicting benefit from strokectomy.CONCLUSIONS: In this study in comparison to former studies, mortality rates were lower and clinical outcome was comparable to that of previously published trials regarding large cerebral infarctions. Second surgery including strokectomy may help achieve better outcomes, especially in cases of infarction of more than one vascular territory.

OBJECTIVE: Cerebral aneurysms (CAs) affect 2%–5% of the population, and familial predisposition plays a significant role in CA pathogenesis. Several lines of evidence suggest that genetic variations in matrix metalloproteinase genes (MMP) are involved in the etiopathology of CAs. The authors performed a case-control study to investigate the effect of 4 MMP variants from the ADAMTS family on the pathogenesis of CAs. METHODS: To identify susceptible genetic variants, the authors investigated 8 single nucleotide polymorphisms (SNPs) in 4 genes from the ADAMTS family (ADAMTS2, -7, -12, and -13) known to be associated with vascular diseases. The study included 353 patients with CAs and 1055 healthy adults. RESULTS: The authors found significant associations between CA susceptibility and genetic variations in 3 members of the ADAMTS family. The largest risk for CA (OR 1.32, p = 0.006) was observed in carriers of the ADAMTS2 variant rs11750568, which has been previously associated with pediatric stroke. Three SNPs under investigation are associated with a protective effect in CA pathogenesis (ADAMTS12 variant rs1364044: OR 0.65, p = 0.0001; and ADAMTS13 variants rs739469 and rs4962153: OR 0.77 and 0.63, p = 0.02 and 0.0006, respectively), while 2 other ADAMTS13 variants may confer a significant risk (rs2301612: OR 1.26, p = 0.011; rs2285489: OR 1.24, p = 0.02). CONCLUSIONS: These results suggest that reduced integrity of the endothelial wall, as conferred by ADAMTS variants, together with inflammatory processes and defective vascular remodeling plays an important role in CA pathogenesis, although the mechanism of action remains unknown. The authors' findings may lead to specific screening of at-risk populations in the future.

Background and Objectives: Simulation-based learning within neurosurgery provides valuable and realistic educational experiences in a safe environment, enhancing the current teaching model. Mixed reality (MR) simulation can deliver a highly immersive experience through head-mounted displays and has become one of the most promising teaching tools in medical education. We aimed to identify whether an MR neurosurgical simulation module within the setting of an undergraduate neurosurgical hands-on course could improve the satisfaction of medical students. Materials and Methods: The quasi-experimental study with 223 medical students [120 in the conventional group (CG) and 103 in the MR-group (MRG)] was conducted at the University Hospital Münster, Münster, Germany. An MR simulation module was presented to the intervention group during an undergraduate neurosurgical hands-on course. Images of a skull fracture were reconstructed into 3D formats compatible with the MR-Viewer (Brainlab, Munich, Germany). Participants could interact virtually with the model and plan a surgical strategy using Magic Leap goggles. The experience was assessed by rating the course on a visual analog scale ranging from 1 (very poor) to 100 (very good) and an additional Likert-scale questionnaire. Results: The satisfaction score for CG and MRG were 89.3 ± 13.3 and 94.2 ± 7.5, respectively. The Wilcoxon rank-sum test showed that MR users (Mdn = 97.0, IQR = 4, n = 103) were significantly more satisfied than CG users (Mdn = 93.0, IQR = 10, n = 120; ln(W) = 8.99, p < 0.001) with moderate effect size (${\widehat{r}}_{biserial}$ = 0.30, CI95 [0.15, 0.43]), thus indicating that the utilization of MR-simulation is associated with greater satisfaction. Conclusions: This study reports a positive response from medical students towards MR as an educational tool. Feedback from the medical students encourages the adoption of disruptive technologies into medical school curricula.

Background: Concepts improving local tumor control in high-grade glioma (HGG) are desperately needed. The aim of this study is to report an extended series of cases treated with a combination of 5-ALA-fluorescence-guided resection (FGR) and intracavitary thermotherapy with superparamagnetic iron oxide nanoparticles (SPION). Methods: We conducted a single-center retrospective review of all recurrent HGG treated with FGR and intracavitary thermotherapy (n = 18). Patients underwent six hyperthermia sessions in an alternating magnetic field and received additional adjuvant therapies on a case-by-case basis. Results: Nine patients were treated for first tumor recurrence; all other patients had suffered at least two recurrences. Nine patients received combined radiotherapy and thermotherapy. The median progression-free survival was 5.5 (95% CI: 4.67–6.13) months and median overall survival was 9.5 (95% CI: 7.12–11.79) months. No major side effects were observed during active treatment. Thirteen patients (72%) developed cerebral edema and more clinical symptoms during follow-up and were initially treated with dexamethasone. Six (33%) of these patients underwent surgical removal of nanoparticles due to refractory edema. Conclusions: The combination of FGR and intracavitary thermotherapy with SPION provides a new treatment option for improving local tumor control in recurrent HGG. The development of cerebral edema is a major issue requiring further refinements of the treatment protocol.