OBJECTIVE Extent of resection (EOR) has previously been demonstrated to have an impact on survival in patients with glioblastoma (GBM). However, with the World Health Organization (WHO) 2021 reclassification of GBMs based on IDH-mutation status, patients with "IDH-mutant GBMs," who typically survive long term, were reclassified as WHO grade 4 IDH-mutant astrocytomas and removed from the GBM taxonomy. Therefore, it is unknown whether the previously reported impact of resection on survival was a false-positive result due to the inclusion of the less aggressive IDH-mutant tumors in previous datasets. This study aimed to determine the extent to which EOR remains an independent predictor of survival in patients with WHO 2021 GBM after the reclassification of IDH-mutant grade 4 astrocytomas. METHODS All cases of GBM tumors (based on the pre-2021 GBM classification) that were newly diagnosed between 2005 and 2021 were identified in our institutional database and subsequently reclassified based on the updated WHO 2021 criteria using IDH status. Multivariable statistical analyses of demographic information, survival time, and EOR based on volumetric MRI were performed to determine the independent predictors of survival for the whole group of patients and for IDH-wildtype GBM patients exclusively. Additional analyses were performed to identify an EOR threshold for improvement in survival. RESULTS Of the 523 tumors classified as GBM based on the pre-2021 taxonomy, 52 (9.9%) cases were reclassified as WHO grade 4 IDH-mutant astrocytomas, and the median survival of patients in this group was 7.9 years, whereas median survival of the IDH-wildtype GBM patients was 1.4 years. Multivariate analyses of the whole group demonstrated that IDH-mutant astrocytomas were associated with reduced hazard of death. In both the whole group (n = 523) and in IDH-wildtype GBMs (n = 471), higher EOR of the contrast-enhancing (CE) tumor was associated with reduced hazard of death, whereas older age or male sex was associated with increased hazard of death. Because most patients (90%) had high EOR values (> 81%), a statistically meaningful EOR threshold could not be established. CONCLUSIONS These analyses demonstrated that EOR of the CE tumor is an independent predictor of survival and that greater EOR is associated with improved survival in WHO 2021 IDH-wildtype GBMs even after excluding grade 4 IDH-mutant astrocytomas. However, an absolute EOR threshold below which resection did not improve survival could not be established, raising concerns about prior cutoff assessments.

The case mix index (CMI) measures the complexity and severity of hospitalized patients and is used to determine hospital reimbursement rates. Better documentation is associated with higher complexity assigned to cases as measured by CMI but remains understudied in the trauma population. The authors hypothesized that standardized templates for neurotrauma history and physical (H&P) notes are associated with increased CMI and reimbursement. A multidisciplinary team consisting of trauma program professionals, trauma data specialists, neurosurgeons, revenue integrity specialists, and financial analysts created traumatic brain injury (TBI) and traumatic spine injury (TSI) H&P templates targeting Medicare Severity Diagnosis Related Groups (MS-DRGs). All neurotrauma cases from 2015 to 2023 were extracted from the electronic medical records with their accompanying diagnosis-related group weights and divided into pretemplate (pre-T) and posttemplate (post-T) groups. The hospital CMI and reimbursement were calculated for the TBI group, the TSI group, and a control group of patients with nonbrain or spine trauma. Comparisons were made between the pre-T and post-T groups. The authors included 5884 neurotrauma patients. TBI and TSI patients were similar in age and sex across time periods. The Injury Severity Score was significantly higher in the post-T period (p < 0.001). CMI was significantly higher for TBI and TSI in the post-T period (2.99 vs 2.51 for TBI, p < 0.001; 4.03 vs 3.42 for TSI, p < 0.001). CMI showed no increase in the post-T period for the nonbrain or spine trauma group (2.41 vs 2.38, p = 0.57). The post-T period demonstrated a significant increase in hospital reimbursement per discharge with a 13% increase for TSI and a 22% increase for TBI. Implementation of a neurotrauma documentation template was associated with increases in hospital CMI and reimbursement for TBI and TSI patients. Further studies are needed to explore how trauma documentation in other subpopulations is associated with hospital CMI and reimbursement.

Approved in 1997, vagus nerve stimulation (VNS) is now a mainstay treatment of refractory epilepsy. While the safety and efficacy of this treatment modality are well established, the authors investigated the patient- and disease-related factors that impact efficacy. The authors conducted a retrospective analysis of 356 patients who underwent VNS therapy at their center from 2000 to 2023. Data collected included age at implantation, age of first seizure, seizure type and etiology, seizure frequency and number of antiseizure medications before and after VNS, presurgical workup, and second surgery after VNS implantation. Responders were classified as those with at least 50% improvement in seizure frequency. Primary outcome was ≥ 50% reduction in seizure frequency. Age at implantation and sex had no significant effect on seizure frequency. Patients with low seizure frequency had a significantly better response than patients with other seizure frequencies. Patients with a baseline seizure frequency of 1-2/year (OR -3.14, 95% CI -5.371 to -0.909) had significantly better outcomes than the other groups, and patients with baseline seizure frequency of 1-2/month also had a significant outcome (OR -1.803, 95% CI -2.875 to -0.730). The authors' study showed no significant difference in VNS outcomes based on known etiology and imaging findings. Patients with 1-2 seizures/year also had a significant decrease in antiseizure medication burden after surgery (p = 0.026). This study showed that patients with refractory epilepsy who experience low baseline seizure frequency (< 1-2/month and < 1-2/year) received the most benefit from VNS. All patients with refractory seizures should be considered for VNS therapy but should undergo careful case selection to manage expectations and maximize seizure outcomes and medication burden.

This study aimed to assess the clinical effectiveness of percutaneous balloon compression (PBC) for trigeminal neuralgia (TN) and develop a predictive model for treatment outcomes. A retrospective analysis was conducted of TN patients who underwent PBC between September 2020 and September 2023. Propensity score matching was used to match ineffective and effective cases at a 1:4 ratio. Perioperative data were analyzed using t-tests and chi-square tests. LASSO (least absolute shrinkage and selection operator) regression identified relevant predictors, which were then used to build a multivariate logistic regression model. Among 230 matched patients, PBC was ineffective in 46 and effective in 184. Perioperative parameters differed significantly between the groups, while demographics did not. Balloon volume, compression duration, balloon pressure, and shape were identified as predictors of treatment outcomes. The model achieved an area under the curve of 0.890, indicating strong discriminative ability. PBC showed significant efficacy in treating TN. Balloon volume, compression duration, pressure, and shape were independent predictors of treatment outcomes.

Peritumoral brain edema (PTBE) of intracranial meningioma (IM) often persists after gross-total resection (GTR) and likely represents reactive gliosis. The authors investigated whether persisting PTBE (i.e., FLAIR hyperintensity) is associated with postoperative seizures and functional outcomes, hypothesizing that it is associated with a higher likelihood of seizures and worse outcomes. The authors retrospectively reviewed all patients (age ≥ 18 years) with IM who underwent GTR at their institution between 2000 and 2020. Included patients had a preoperative MRI study showing PTBE and at least a 2-year MRI follow-up. Univariable and multivariable analyses identified factors associating with seizures and functional outcome (Karnofsky Performance Status [KPS]). Postoperative electroencephalography (EEG), when available, was reviewed to locate epileptogenic foci. Among 218 adult IM patients with preoperative PTBE, preoperative seizures occurred in 94 (43.1%). Seizures persisted in 27 (28.7%) patients after surgery (mean time to first postoperative seizure 8.4 months). Of the 124 patients without preoperative seizures, 18 (14.5%) developed new-onset postoperative seizures (mean time to first seizure 7.6 months). Persisting PTBE volume in the highest tertile (median 12.8 cm3, range 6.7-54.0 cm3) was associated (p = 0.03, OR 4.7) with new-onset seizures in comparison with the lowest tertile (median 0.5 cm3, range 0.0-1.6 cm3). An increase in postoperative PTBE volume was also associated with new-onset seizures (p = 0.008, OR 6.7) and persisting seizures (p = 0.004, OR 4.4). Postoperative EEG was available for 23 patients, of whom 10 (43.5%) had an epileptogenic focus at the site of persisting PTBE. Larger persisting PTBE volumes were associated with worse postoperative KPS (p = 0.04, OR 1.03 per cm3 increase). Persisting PTBE is associated with worse functional outcome and with persisting and new-onset seizures. Based on EEG findings, persisting PTBE (i.e., gliosis) may be the epileptogenic focus in some patients. Future studies are needed to assess whether these gliotic sites could even be therapeutic targets for seizure control.

Intracranial aneurysm (IA) is a leading cause of subarachnoid hemorrhage, characterized by complex pathogenesis and high mortality rates due to rupture. The aim of this study was to develop a targeted glucagon-like peptide-1 (GLP-1) nanodelivery system to mobilize endothelial progenitor cells (EPCs) and enhance re-endothelialization in a rat model of coiled IA. In this study, a matrix metalloproteinase-2 (MMP-2)-targeted nanodelivery platform (hereafter GLP-1@tMSN [targeted mesoporous silica nanoparticle]) based on MSNs functionalized with GLP-1 was developed to mobilize EPCs and accelerate vascular repair. The efficacy of GLP-1@tMSN in promoting EPC recruitment and re-endothelialization was evaluated in a rat coiled aneurysm model, alongside mechanistic studies of the Wnt/β-catenin signaling pathway. In a rat model of coiled IA, GLP-1@tMSN significantly enhanced the recruitment of EPCs and promoted re-endothelialization. Histological analysis demonstrated the formation of mature endothelial-like tissue after 28 days, in contrast to the fibrous tissue observed in the control group. Immunofluorescence analysis confirmed the preferential accumulation of CD34+VEGFR2+ EPCs at the lesion site, with concurrent activation of the Wnt/β-catenin pathway, implicating its pivotal role in driving vascular repair. Preliminary safety evaluations further indicated a favorable biocompatibility profile for the nanotherapeutic system. The developed functionalized nanodelivery platform represents a promising therapeutic strategy to enhance localized GLP-1 efficacy, facilitating rapid re-endothelialization and potentially reducing long-term recurrence of IAs after embolization. This approach shows substantial potential for improving outcomes for patients with IA.

Managing large posterior fossa brain metastases (PFBMs) poses significant challenges. Although staged stereotactic radiosurgery (SRS) is an effective and minimally invasive alternative for large brain metastases, its clinical utility for large PFBMs has not yet been fully elucidated. The aim of this study was to evaluate the safety and efficacy of staged SRS in the treatment of large PFBMs. This retrospective analysis included patients who underwent upfront staged SRS for PFBMs measuring 4 mL or larger between 2010 and 2024 at a single tertiary cancer center. Patients who had received prior local treatment were excluded from the study. The radiosurgical protocol encompassed delivering 24-30 Gy in 2 fractions, with a time interval of 3-4 weeks between sessions. Outcome measures, including overall survival, local control of large PFBMs, and leptomeningeal metastasis (LM), were assessed using time-dependent analyses, considering competing events when appropriate. A consecutive cohort of 92 patients (49 male, median age 68 years) with 96 large PFBMs was included in the study. Primary cancers were small cell lung cancer, non-small cell lung cancer, and colorectal, breast, genitourinary, and upper digestive tract cancers in 11, 30, 24, 16, 7, and 4 patients, respectively. Eighty-two patients (89%) exhibited neurological symptoms, and the median volume of large PFBMs was 9.0 mL. At the time of the second session, the median PFBM volume had decreased by 49% to 4.6 mL. During the treatment interval, 2 patients underwent urgent craniotomies due to tumor bleeding and obstructive hydrocephalus. The 1- and 2-year overall survival rates following staged SRS were 51% and 30%, respectively (median 12.2 months). The 1- and 2-year local failure rates for large PFBMs were 17% and 23%, respectively. Rapid tumor response (defined as a 50% or greater volume reduction at the second session) was the sole factor associated with higher probability of local tumor control (HR 0.32, 95% CI 0.12-0.86; p = 0.024). The mean Karnofsky Performance Status (KPS) score improved from 71 at the first SRS session to 85 at the second; the first follow-up mean KPS score was 90 (p < 0.001). The 1- and 2-year LM rates remained low at 11% and 14%, respectively. These results suggest that staged SRS is a safe and less invasive treatment option for selected patients with PFBMs larger than 4 mL, achieving reasonable local control rates and low LMs rates in the long term.

Pial arteriovenous fistulas (AVFs) are rare cerebrovascular shunts characterized by direct connections between pial arteries and veins. Despite increasing recognition in adults, their anatomical features and clinical implications remain poorly understood. The authors aimed to characterize the clinical and radiological features of adult intracranial pial AVFs, propose an angioarchitectural classification, and assess treatment outcomes. The authors conducted a nationwide, multicenter, retrospective cohort study of adult intracranial pial AVFs in Japan between 2013 and 2024. Imaging data were centrally reviewed to confirm diagnoses and classify lesions based on angioarchitecture. Lesions were defined as microfistulas when the diameter of the shunt feeder was < 2 mm and as macrofistulas when it was ≥ 2 mm. Clinical features, treatment strategies, and outcomes were compared descriptively between the groups. A total of 66 patients with 72 pial AVFs were analyzed. Compared with macrofistulas, microfistulas were more common (74.2%) and occurred more often in older patients (median age 66 vs 32 years, p < 0.001). Furthermore, dural AVFs (42.9% vs 5.9%, p = 0.006) and a history of cerebrovascular events (24.5% vs 0%, p = 0.027) were more frequently observed in microfistulas. Varix formation and multiple draining veins were commonly seen in macrofistulas (94.7% vs 7.5%, p < 0.001 and 21.1% vs 0%, p = 0.004, respectively). Among 72 lesions, 70.8% underwent intervention, with transarterial embolization being the most common modality (51.0%). Complete obliteration was achieved in 78.4% of treated cases. Each lesion was further subclassified into distinct subtypes based on angioarchitectural configuration. One macrofistula subtype (5.6%), characterized by multiple feeders connecting to different multiple draining veins, showed lower obliteration rates and higher complication rates in the few treated cases. Adult pial AVFs exhibit considerable angioarchitectural heterogeneity, which may relate to variations in clinical presentation and management. Our proposed classification scheme may provide a descriptive framework for characterizing these lesions, although further validation is needed.