Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hydrocephalus after Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannomas is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on hydrocephalus risk remains poorly defined. METHODS:A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® SRS for unilateral vestibular schwannomas from 2011 to 2021 was performed. Patients with prior hydrocephalus and cerebrospinal fluid diversion or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)-maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull-were measured on axial postcontrast T1-weighted magnetic resonance imaging. RESULTS:A total of 378 patients met the inclusion criteria; 14 patients (3.7%) developed symptomatic communicating hydrocephalus and 10 patients (2.6%) underwent shunt placement and 4 patients (1.1%) were observed with milder symptoms. The median age of patients who developed hydrocephalus was 69 years (IQR, 67-72) and for patients younger than age 65 years, the risk was 1%. For tumor volumes <1 cm3, the risk of requiring shunting was 1.2%. The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (P = .024) and tumor volume >3 cm3 (P = .007), respectively, in multivariate analysis. Fourth ventricle distortion on pre-SRS imaging was significantly associated with hydrocephalus incidence (P < .001). CONCLUSION/CONCLUSIONS:Patients with vestibular schwannoma with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. These patients should be counseled regarding risk of hydrocephalus and carefully monitored after SRS.

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability between treatment groups. After PSM, 90 patients were allocated to each treatment group. Significant differences were observed in complete obliteration rates, with resection achieving higher rates compared to SRS in overall cases (97.8% vs. 60.0%, p < 0.001), unruptured AVMs (100% vs. 58.3%, p < 0.001), and ruptured AVMs (95.2% vs. 61.9%, p < 0.001). Functional improvement rates were similar between the groups for overall cases (67.2% in resection vs. 66.7% in SRS, p = 0.95), unruptured AVMs (55.2% in resection vs. 55.6% in SRS, p > 0.9), and ruptured AVMs (78.1% in resection vs. 74.1% in SRS, p = 0.7). Symptomatic complication rates were identical between the groups (11.1% each, p > 0.9), while permanent complication rates were comparable (6.7% in resection vs. 5.6% in SRS, p = 0.8). Resection demonstrated significantly higher complete obliteration rates compared to SRS across all cases, including unruptured and ruptured AVMs. Functional improvement rates were similar between the two treatment groups, with no significant differences in symptomatic or permanent complication rates.

Seizures occur in 20-45% of patients with cerebral arteriovenous malformations (AVMs) and can potentially influence their quality of life. Some studies have suggested risk factors influencing their development, but the evidence is limited to small cohorts. To analyze seizure presentation and factors influencing seizure development in patients with cerebral AVMs using a multi-institutional consortium. Retrospective multicenter registry from multiple centers in North America and Europe of patients aged 1 to 89 years who had undergone any intervention for brain AVMs between January 2010 and December 2023. Demographics, functional assessment (modified Rankin Scale; mRS), and AVM characteristics, were evaluated to assess for relationship with seizures using a multivariate generalized linear mixed-effects model. 1,005 AVM patients were analyzed; the median age was 42, 73% had a baseline mRS ≤ 2. The median nidus size was 2.2 cm, and most AVMs were Spetzler-Martin grade II (37%). Seizure was the presenting symptom in 237 patients (24%). After adjusting for significant variables, patient-specific factors associated with seizures were younger age (OR 0.99, CI95% 0.98-1), male sex (OR 1.65, CI95% 1.18-2.30), and smoking history (OR 1.69, CI95% 1.17-2.44). AVM-specific factors associated with seizures included rupture status (OR 0.42, CI95% 0.30-0.61); eloquent cortex (OR 1.61, CI95% 1.13-2.29); frontal (OR 1.54, CI95% 1.01-2.35), temporal (OR 1.93, CI95% 1.26-2.96) and parietal (OR 1.71 CI95% 1.08-2.71) location; larger nidal size (OR = 1.23, CI95% 1.08-1.39), and superficial draining vein location (OR 1.86, CI95% 1.15-3.01). In this multicenter consortium, after controlling for significant variables, the incidence of AVM-related seizures was associated with younger age, male sex, smoking history, larger AVMs, eloquent locations, and AVMs in the frontal, temporal, and parietal cortices. Conversely, rupture status, deep venous drainage, and cerebellar locations were negatively associated with seizures.

INTRODUCTION/UNASSIGNED:The impact of multiple feeding arteries on clinical outcomes of cerebral arteriovenous malformations (AVMs) is not well understood. This study aims to compare outcomes between AVMs with multiple versus single feeding arteries. PATIENTS AND METHODS/UNASSIGNED:Data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium were analyzed. Propensity score matching (PSM) was used to balance cohorts. Subgroup analysis was conducted for ruptured and unruptured AVMs and different treatment options, and multivariable logistic regression was applied to assess the impact of feeding artery origin. RESULTS/UNASSIGNED: = 0.002). DISCUSSION AND CONCLUSION/UNASSIGNED:AVMs with a single feeding artery were more likely to present with rupture, but no significant differences in obliteration rates or complications were observed between the groups after PSM. These findings suggest that while the number of feeding arteries may influence the initial presentation, it does not appear to impact overall treatment success or patient prognosis. Further prospective studies are needed to confirm these findings.

BACKGROUND:Arteriovenous malformations (AVMs) are complex vascular anomalies with a high risk of hemorrhage and neurological deficits, especially when located in eloquent brain regions. The eloquence of an AVM location is a critical factor in the treatment planning, influencing both the risk of complications and long-term functional outcomes. This study aims to compare outcomes between eloquent and non-eloquent AVMs. METHODS:This multicenter, retrospective study utilized data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium. Patients with eloquent and non-eloquent AVMs were compared on baseline characteristics, angiographic outcomes, and functional outcomes using the modified Rankin Scale (mRS). Propensity score weighting (IPTW) was applied to adjust for confounding variables. RESULTS:The study included 1,013 patients, with 498 (49.2%) AVMs located in eloquent regions and 515 (50.8%) in non-eloquent regions. In unadjusted analysis, eloquent AVMs had lower complete obliteration rates (67.6% vs. 79.5%, OR: 0.53, 95% CI: 0.39-0.72, p < 0.001) and higher complication rates (24.5% vs. 19.0%, OR: 1.38, 95% CI: 1.02-1.86, p = 0.03) compared to non-eloquent AVMs. After IPTW adjustment, eloquent AVMs continued to show significantly higher odds of overall complications (OR: 1.68, 95% CI: 1.12-2.52, p = 0.01) and symptomatic complications (OR: 1.77, 95% CI: 1.12-2.80, p = 0.01). Secondary analysis within the eloquent group indicated that embolization was linked to an elevated risk of complications. Surgery and radiosurgery showed comparable functional outcomes at last follow-up and complications rates with higher complete obliteration rates in surgery. CONCLUSION/CONCLUSIONS:AVMs in eloquent brain areas present higher risks of complications and lower obliteration rates, emphasizing the need for cautious, individualized treatment planning. Within the eloquent group, embolization increased the risk of complications, while surgery and radiosurgery showed comparable functional outcomes at last follow-up and complication rates with higher complete obliteration rates in surgery. These findings highlight the importance of location in AVM management and support further research focusing on comparing treatment strategies for AVMs in eloquent brain areas.

The adoption of large language models (LLMs) in healthcare demands a careful analysis of their potential to spread false medical knowledge. Because LLMs ingest massive volumes of data from the open Internet during training, they are potentially exposed to unverified medical knowledge that may include deliberately planted misinformation. Here, we perform a threat assessment that simulates a data-poisoning attack against The Pile, a popular dataset used for LLM development. We find that replacement of just 0.001% of training tokens with medical misinformation results in harmful models more likely to propagate medical errors. Furthermore, we discover that corrupted models match the performance of their corruption-free counterparts on open-source benchmarks routinely used to evaluate medical LLMs. Using biomedical knowledge graphs to screen medical LLM outputs, we propose a harm mitigation strategy that captures 91.9% of harmful content (F1 = 85.7%). Our algorithm provides a unique method to validate stochastically generated LLM outputs against hard-coded relationships in knowledge graphs. In view of current calls for improved data provenance and transparent LLM development, we hope to raise awareness of emergent risks from LLMs trained indiscriminately on web-scraped data, particularly in healthcare where misinformation can potentially compromise patient safety.

BACKGROUND:Spetzler-Martin (SM) Grade III brain arteriovenous malformations (BAVMs) represent a transitional risk zone between low- and high-grade BAVMs, characterized by diverse angioarchitecture. The primary treatment options are endovascular embolization, microsurgical resection (MS), and stereotactic radiosurgery (SRS). This study compares the efficacy and outcomes of MS and SRS. METHODS:We conducted a multicenter, retrospective study involving patients from the MISTA database with SM Grade III BAVMs treated with MS or SRS between 2010 and 2023. Propensity matching was based on age, favorable modified Rankin Score (mRS) at presentation, nidus size, rupture status, location depth, and eloquence. RESULTS:, p = 0.6) were similar. MS showed higher obliteration rates (93.3 %) compared to SRS (46.7 %) at the last follow-up (p < 0.001). The median time to obliteration post-SRS was 31.5 months (IQR: 15.3-60.0). SRS obliteration rates were 19 %, 29 %, and 59 % at 24, 36, and 60 months, respectively. Overall complication rates (MS: 30 % vs. SRS: 20 %, p = 0.4) and permanent complications (MS: 10 % vs. SRS: 13.3 %, p > 0.9) were similar. Hemorrhage occurred once in the MS group and none in the SRS (p > 0.9). Favorable outcomes (mRS 0-2) were higher with SRS than MS (93.3 % vs 80.0 %, p = 0.3), with one AVM-related mortality in the MS group. CONCLUSION/CONCLUSIONS:MS and SRS are viable treatments for SM Grade III BAVMs. Treatment choice should be individualized by a multidisciplinary team, considering patient goals.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Scholarly output is accelerating in medical domains, making it challenging to keep up with the latest neurosurgical literature. The emergence of large language models (LLMs) has facilitated rapid, high-quality text summarization. However, LLMs cannot autonomously conduct literature reviews and are prone to hallucinating source material. We devised a novel strategy that combines Reference Publication Year Spectroscopy-a bibliometric technique for identifying foundational articles within a corpus-with LLMs to automatically summarize and cite salient details from articles. We demonstrate our approach for four common spinal conditions in a proof of concept. METHODS:Reference Publication Year Spectroscopy identified seminal articles from the corpora of literature for cervical myelopathy, lumbar radiculopathy, lumbar stenosis, and adjacent segment disease. The article text was split into 1024-token chunks. Queries from three knowledge domains (surgical management, pathophysiology, and natural history) were constructed. The most relevant article chunks for each query were retrieved from a vector database using chain-of-thought prompting. LLMs automatically summarized the literature into a comprehensive narrative with fully referenced facts and statistics. Information was verified through manual review, and spine surgery faculty were surveyed for qualitative feedback. RESULTS:Our tandem approach cost less than $1 for each condition and ran within 5 minutes. Generative Pre-trained Transformer-4 was the best-performing model, with a near-perfect 97.5% citation accuracy. Surveys of spine faculty helped refine the prompting scheme to improve the cohesion and accessibility summaries. The final artificial intelligence-generated text provided high-fidelity summaries of each pathology's most clinically relevant information. CONCLUSION/CONCLUSIONS:We demonstrate the rapid, automated summarization of seminal articles for four common spinal pathologies, with a generalizable workflow implemented using consumer-grade hardware. Our tandem strategy fuses bibliometrics and artificial intelligence to bridge the gap toward fully automated knowledge distillation, obviating the need for manual literature review and article selection.

PURPOSE/OBJECTIVE:The purpose of this study was to investigate an extended self-adapting nnU-Net framework for detecting and segmenting brain metastases (BM) on magnetic resonance imaging (MRI). METHODS AND MATERIALS/METHODS:Six different nnU-Net systems with adaptive data sampling, adaptive Dice loss, or different patch/batch sizes were trained and tested for detecting and segmenting intraparenchymal BM with a size ≥2 mm on 3 Dimensional (3D) post-Gd T1-weighted MRI volumes using 2092 patients from 7 institutions (1712, 195, and 185 patients for training, validation, and testing, respectively). Gross tumor volumes of BM delineated by physicians for stereotactic radiosurgery were collected retrospectively and curated at each institute. Additional centralized data curation was carried out to create gross tumor volumes of uncontoured BM by 2 radiologists to improve the accuracy of ground truth. The training data set was augmented with synthetic BMs of 1025 MRI volumes using a 3D generative pipeline. BM detection was evaluated by lesion-level sensitivity and false-positive (FP) rate. BM segmentation was assessed by lesion-level Dice similarity coefficient, 95-percentile Hausdorff distance, and average Hausdorff distance (HD). The performances were assessed across different BM sizes. Additional testing was performed using a second data set of 206 patients. RESULTS:. Mean values of Dice similarity coefficient, 95-percentile Hausdorff distance, and average HD of all detected BMs were 0.758, 1.45, and 0.23 mm, respectively. Performances on the second testing data set achieved a sensitivity of 0.907 at an FP rate of 0.57 ± 0.85 for all BM sizes, and an average HD of 0.33 mm for all detected BM. CONCLUSIONS:Our proposed extension of the self-configuring nnU-Net framework substantially improved small BM detection sensitivity while maintaining a controlled FP rate. Clinical utility of the extended nnU-Net model for assisting early BM detection and stereotactic radiosurgery planning will be investigated.