bluuebunny/crossref_metadata_2025_split huggingface dataset:
199 Gamma Knife Radiosurgery to Treat Neurofibromatosis Type 2-Associated Meningiomas: A 35 Year Experience and Paradigm for Future Treatment
Authors: Niranjan Ajay , Wei Zhishuo , Taori Suchet , Alamer Othman Bin , Abou-Al-Shaar Hussam , Hadjipanayis Constantinos G. , Lunsford L. Dade 
Published: March 2024

INTRODUCTION:
Management of neurofibromatosis type 2 (NF2)-associated meningiomas remains a case-by-case basis, and treatment options vary.

METHODS:
Forty-nine patients (22 male, 44.90%) with 213 NF2-associated meningiomas treated with SRS between 1987 and 2022 were retrospectively reviewed. The median age at SRS was 56 (range: 20-79) years. Twenty-nine (59.18%) patients had pre-SRS surgical resection, and 7 (14.29%) had prior radiotherapy. The median number of meningiomas per patient was 2 (range: 1-17), the median margin dose was 13 (range: 9-16) Gy, and the median cumulative tumor volume per patient was 8.30 (range: 0.10-74.26) cm3.

RESULTS:
Nine patients (18.37%) had local tumor progression. The 1- and 5-year local tumor control rates were 100% and 90.54%, respectively. Tumor volume < 8.30 cm3 was associated with better local tumor control (p = 0.02, HR: 1.06, 95% CI: 1.01-1.12) on multivariate analysis. Twenty-five patients (51.02%) had detection of new growing tumors (DNGT). The 1- and 5-year DNGT rates were 78.05% and 47.38%, respectively. On multivariate analysis, >2 meningiomas at SRS presentation per patient (p = 0.01, HR: 1.09, 95% CI: 1.02-1.17) was significantly associated with DNGT. Neurological symptoms improved in 20 patients (40.82%), remained stable in 28 patients (57.14%), and worsened in 1 (2.04%) patient at a median follow-up time of 81 (range: 6–267) months after SRS. Seventeen (34.69%) patients were deceased at last follow-up, and 4 patients expired due to intracranial disease progression. Two (4.08%) patients developed transient adverse radiation effects; no patients developed secondary malignancies.

CONCLUSIONS:
Single-session SRS can effectively be used to control tumor progression and improve neurological symptoms in NF2-associated meningioma patients while limiting adverse radiation effects.
201 Clear Cell Meningioma Tumorigenesis Is Characterized by Expression of Human Endogenous Retroviruses
Authors: DeBacker Dang Danielle , Doucet-O'Hare Tara , Rosenblum Bruce S. , Mohlin Sofie , Shah Ashish H. , Winson Ho Sze Chun , Vortmeyer Alex , McGavern Dorian , Heiss John D. , Zhuang Zhengping 
Published: March 2024

INTRODUCTION:
Human endogenous retroviruses (HERVs) are transcriptionally silenced genetic remnants of ancient exogenous retroviruses in differentiated cells yet critical to early tissue development. We recently found that aberrant expression of HERV-K envelope protein, caused by SMARCB1 mutation, is critical for tumorigenesis in atypical teratoid rhabdoid tumor (AT/RT). Clear cell meningioma (CCM) demonstrates analogous altered chromatin remodeling via SMARCE1 loss of function and syncytial histopathologic features thereby indicating a putative role for HERV expression in CCM tumorigenesis.

METHODS:
Eight CCM samples were evaluated for SMARCE1 status. We then quantified expression of HERV-K envelope and OCT-4 protein, a marker of pluripotency, by immunohistochemistry and compared them using linear regression. Active HERV transcript production was evaluated by RNA in-situ hybridization. Finally, we induced SMARCE1 loss in neural stem cells (NSC’s) and assessed expression of multiple HERV transcripts. We further modeled SMARCE1 knock-down in vivo in a chicken embryo model to evaluate timing of aberrant HERV expression and CCM development.

RESULTS:
All CCM tumor samples demonstrated loss of SMARCE1 and expression of HERV-K-Env and OCT-4 proteins and HERV transcripts. Expression was more robust in syncytial tumor-initiating cells and surrounding extracellular vesicles. HERV-K-Env expression positively correlated with OCT-4 expression (Pearson’s R = 0.7461, p = 0.033). Finally, SMARCE1 knock-down in NSC's and chicken embryos resulted in expression of multiple HERVs, supporting SMARCE1 loss of function as the mechanism of increased HERV expression in our CCM cohort.

CONCLUSIONS:
As mediated by loss of SMARCE1 function, HERV transcription allows for pathogenic exportation of HERV proteins to surrounding cells to maintain pluripotency in both in vitro and in vivo models. Aberrant HERV expression may therefore represent a targetable anticancer pathway for CCM and similar CNS tumors.
202 The Role of Surgical Management for Prolactinoma in the Era of Dopaminergic Agonists: An International Multicenter Report
Authors: Findlay Matt , Sabahi Mohammadmahdi , Azab Mohammed , Drexler Richard , Rotermund Roman , Ricklefs Franz Lennard , Flitsch Jörg , Smith Timothy R. , Kilgallon John , Honegger Jürgen , Nasi-Kordhishti Isabella , Gardner Paul A. , Charl Zachary 
Published: March 2024

INTRODUCTION:
Although first-line prolactinoma (PL) management typically involves dopamine agonists (DAs), the role of surgery as a primary therapeutic is being reconsidered given the undesirable side effects of long-term DAs.

METHODS:
Patients surgically treated for PL from January 2017 through December 2020 were identified. Preoperative characteristics and postoperative outcomes were assessed. Multivariate models adjusting for tumor characteristics and surgery complexity identified factors predictive of complications and long-term adverse outcomes.

RESULTS:
Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PLs were macroadenomas. Most PLs were managed microscopically (69.9%) and fewer endoscopically (29.0%). Although 29.8% of patients experienced at least one early postoperative complication, most were minor (39.3%), with less being major complications (4.4%). The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. Based on available data on follow-up, disease remission on long-term follow-up imaging was achieved in 94.8% of cases, and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. Upon multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly prohibitive against long-term endocrinological cure. Knosp classification was highly predictive of residual tumor or PL recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01).

CONCLUSIONS:
Our results evaluate a modern, multicenter, global series of patients treated for PL. This data serves as a benchmark to compare with DAs and demonstrates that surgery offers high rates of remission with low rates of complications and recurrence. It may be reasonable to consider surgery as an alternative to DAs.
203 RNA Polymerase II Meningioma Mutations Activate Forebrain Neurodevelopmental Pathways
Authors: Clark Victoria Elizabeth , Prager Briana , Wilson-Hawken Susana , Young Richard 
Published: March 2024

INTRODUCTION:
RNA polymerase II, which transcribes DNA into RNA, is mutated in a subset of skull base meningiomas. Patient-derived Pol II mutant meningiomas are dysregulated in pathways directing neural crest differentiation and neurodevelopment. The molecular mechanism of the Pol II driver mutation has remained elusive, and may provide novel therapeutic insight.

METHODS:
The POLR2A Q403K meningioma driver mutation was modeled in the mouse embryonic stem cell system using CRISPR-Cas9. Metabolic labeling of nascent RNA was performed with 4-thiouridine (SLAMseq). Pol II ChIPseq was performed to calculate the travel ratio (proportion of initiated Pol II to elongating Pol II). POLR2A Q403K and wildtype mES cells differentiated over 12 days in permissive media, RNA was harvested over multiple days, and RNAseq was performed.

RESULTS:
POLR2A Q403K cells had a global increase in transcription per nascent RNA sequencing, as measured by T>C conversions (p = 5.71x10-66). For active and highly-paused genes, which were enriched for neurodevelopmental pathways (FDR = 3.52x10-25), a left shift in the mean travel ratio revealed defects in pause-release as the mechanism for increased levels of nascent transcription. Recapitulating human disease, POLR2A Q403K mES cells had significant activation of Hedgehog (Padj. = 2.4x10-3) and WNT (Padj. = 5.2x10-3) signaling pathways, and by day 12 of differentiation showed significant upregulation of pathways critical for rostral cortical development including forebrain neuronal differentiation (FDR = 4.86x10-4), telencephalon development (FDR = 4.30x10-4), and neuronal differentiation (FDR = 4.39x10-4).

CONCLUSIONS:
Meningioma Pol II mutations drive global increases in transcription via dysregulation of pause-release. Highly-paused genes, including master regulators of neural development, are disproportionately activated by mutant Pol II. This dysregulation leads to aberrant induction of neurodevelopmental signaling, including Hedgehog and WNT, and provides a rationale for pharmacologic targeting of these pathways.
205 Microglia-Mediated Survival Outcomes in Preoperative Radiation for Glioblastoma: Insights From a Preclinical Model
Authors: Otamendi-Lopez Andrea , Fernandez Gil Beatriz Irene , Vazquez-Ramo Carla A , Cherukuri Yesesri , Herchko Steven , Jentoft Mark E. , Murray Melissa , Asmann Yan , Trifiletti Daniel M. , Sarabia-Estrada Rachel , Quinones-Hinojosa Alfredo 
Published: March 2024

INTRODUCTION:
Glioblastoma (GBM) is the most common and devastating primary brain tumor in adults. The current standard of care includes maximal safe resection followed by concurrent radiation and temozolomide-based chemotherapy. However, preoperative radiotherapy is used in different cancer types and commonly used for brain metastasis to shrink tumors, but it has never been used in for primary GBM.

METHODS:
Thirty-nine immunocompromised adult athymic nude female rats were orthotopically engrafted with a GBM1A patient-derived glioma cell line and randomized to either receive radiotherapy prior to tumor resection (RTRE) or postoperative radiotherapy (RERT). The rats received 30 Gy hypofractionated stereotactic radiation in 5 fractions of 6 Gy. Kaplan-Meier curve was used to plot the survival. Hematoxylin-eosin staining, microglia/macrophages using IBA-1 and TMEM119 markers were used in resected and recurrent tumor tissues. Moreover, nuclei area was measured on all tumor samples. Student’s T-test and analysis of variance (ANOVA) were used for statistical analysis.

RESULTS:
Kaplan-Meier analysis showed a significant survival benefit in the RTRE group, with median survival of 18.28 weeks compared to 14.85 weeks for RERT (p < 0.001), which correlated with the time of recurrence. Simultaneously, an increase in the nuclei area was found in the resected tumor tissues from the RTRE group (p < 0.001) and RERT recurrent tumor tissues (p < 0.001). Interestingly, we found lower microglia/macrophage recruitment in RTRE in the recurrent tumors (p < 0.01) and throughout the tumor areas compared to the RERT group.

CONCLUSIONS:
Our study represents the first preclinical study demonstrating the feasibility and longer overall survival using RTRE instead of RERT in vivo. Moreover, RTRE shows an important effect in the macrophages/microglia recruitment and in the immune profile. This suggests strong superiority for new clinical radiation strategies.
212 Differential Immune Cell Recruitment Between Ruptured and Unruptured Intracranial Aneurysms
Authors: Lucke-Wold Brandon 
Published: March 2024

INTRODUCTION:
Accumulating evidence implicates infiltrating inflammatory cells in intracranial aneurysms. However, few studies have examined immunological differences between aneurysm rupture statuses.

METHODS:
An established machine-learning deconvolution algorithm was applied on RNA-sequencing data developed from vessel wall tissue of 21 ruptured and 21 unruptured intracranial aneurysms. A validated gene signature matrix of human hematopoietic cell subsets was used to infer the relative fractions of immune cells present within the original aneurysm tissues.

RESULTS:
Deconvolution of the bulk gene expression data showed significantly increased plasma cells, CD8+ T cells, and activated natural killer cells in unruptured aneurysms compared to ruptured aneurysms.

CONCLUSIONS:
Specific lymphoid elements may be involved in an inflammatory reaction prior to intracranial aneurysm rupture.
214 Technical and Clinical Outcomes in Patients With Short-term Repeated Mechanical Thrombectomy: An International Multicenter Study
Authors: Saad Hassan , Zohdy Youssef M. , Howard Brian M. , Cawley C. Michael , Pabaney Aqueel Hussain , Dimisko Laurie , Alawieh Ali M. , Maier Ilko , Spiotta Alejandro M. , Jabbour Pascal , Wolfe Stacey Q. , Rai Ansaar , Kim Joon-Tae , Masitelli Justin Robert , Starke Robert M. , Shaban Amir , Yoshimura Shinichi , De Leacy Reade , Kan Peter T. , Fragata Isabel , Polifka Adam J. , Arthur Adam S. , Park Min S. , Matouk Charles , Levitt Michael Robert , Tjoumarkaris Stavropoula I. , Liman Jan , Fargen Kyle Michael , Grossberg Jonathan Andrew 
Published: March 2024

INTRODUCTION:
Endovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat EVT (rEVT) in recurrent LVO remains unclear.

METHODS:
Data were included from the Stroke Thrombectomy and Aneurysm Registry (STAR) with 21 stroke centers for EVT performed to treat LVO stroke from 2013-2022. Patients undergoing single or rEVT within 30 days were included. Propensity score matching was used to compare patients undergoing single versus rEVT. The primary outcome was the modified Rankin score(mRS) at 90 days, and secondary outcomes were successful recanalization, postprocedural hemorrhage and mortality.

RESULTS:
Out of a total of 7387 patients who underwent EVT for LVO stroke, 90(1.2%) patients underwent rEVT for the same vascular territory within 30 days. The average time to re-occlusion was 5.3±7.3 days, and 41(45.6%) patients required rEVT within 24hrs. Patients undergoing rEVT had comparable rate of good functional outcome and mortality rate, but with but higher rate of symptomatic intracranial hemorrhage compared to a matched cohort of patients undergoing single procedure. There was a significant reduction in NIHSS before rEVT and at discharge (ΔNIHSS=(-)5 ± 1; p = 0.006). The rate of successful recanalization was similar in single and rEVT groups (78% versus 80%, p = 0.78) and between index and rEVT performed on the same patients (79% versus 80%; p = 0.78).

CONCLUSIONS:
Short-term rEVT is associated with comparable functional outcomes but with higher rate of hemorrhagic conversion compared to patients undergoing single EVT.
216 Loss of Endothelial Tissue-Nonspecific Alkaline Phosphatase Exacerbates Microhemorrhages and Neuroinflammation in a Mouse Model of Ischemic Stroke
Authors: Nwafor Divine , Clary Briana , Al-Humaire Muna , Brown Candice 
Published: March 2024

INTRODUCTION:
Despite significant progress in treatment strategies, stroke remains a leading cause of mortality and morbidity. Blood-brain barrier dysfunction is coupled to neuroinflammation and poor outcomes post-stroke. Tissue-nonspecific alkaline phosphatase (TNAP) is a glycophosphatidylinositol-linked protein localized to brain microvascular endothelial cells (BMECs). However, TNAP’s role in BMECs remains unclear. Recent in vitro data from our laboratory demonstrates that conditional loss of BMEC TNAP significantly worsened barrier integrity. Importantly, we have shown that TNAP activity is significantly reduced on cerebral microvessels in the penumbra of wild-type stroke mice.

METHODS:
To test this, we generated mice with a conditional deletion of TNAP in endothelial cells (VE-cKO) and compared the results to controls (Alplfl/fl). Six-month-old mice underwent photothrombotic ischemic stroke (PTS) or sham surgery.

RESULTS:
Laser speckle flowmetry confirmed that PTS mice exhibited a sustained loss of cerebral blood flow compared to sham mice (p < 0.0001). No significant differences in cerebral blood flow and infarct size were noted between VE-cKO PTS and Alplfl/fl PTS mice. Seven days post-PTS, mice were euthanized, and brains were evaluated for BBB dysfunction and neuroinflammation. Preliminary evidence demonstrates a significant increase (p < 0.0001) in GFAP-positive astrogliosis in the cortical penumbra of VE-cKO PTS compared to Alplfl/fl PTS mice. Astrogliosis was also coupled to a significant increase in the number of microhemorrhages (p < 0.0001) in VE-cKO PTS compared to Alplfl/fl PTS mice. Interestingly, large molecule BBB permeability evaluation with immunoglobulin G (150 kDa) showed no significant differences between VE-cKO PTS and Alplfl/fl PTS mice.

CONCLUSIONS:
Ongoing studies will quantitatively assess the extent of BBB permeability utilizing fluorescent tracers of varying sizes. Collectively, these results support a novel mechanism through which loss of TNAP activity is linked to brain microvascular dysfunction post-stroke.
217 Early Experience With Robotic Microvascular Anastomoses
Authors: Wiggan Daniel , Rabbin-Birnbaum Corinne , Sangwon Karl Lee , Choudhry Osamah J. , Nossek Erez 
Published: March 2024

INTRODUCTION:
Robotics are becoming increasingly widespread within various neurosurgical subspecialties. The adoption of robotic technology within vascular neurosurgery is of great interest, but data pertaining to its feasibility is currently limited.

METHODS:
68 sutures were performed and assessed. 6 anastomoses (3 robotic and 3 hand-sewn) were performed on 1-1.5 mm caliber tubes and recorded with the operative microscope. We separately compared interrupted sutures (from needle insertion until third knot) and running sutures (from needle insertion until stitch pull-out). Average suture timing across all groups was compared using an unpaired student’s T test.

RESULTS:
We compared 29 robotic sutures to 39 hand-sewn sutures. There was no significant difference between the average time/stitch for the robotic running sutures (n = 18) and the hand-sewn running sutures (n = 16) (45.6 s vs. 41.2 s; p-value = 0.3). The average for the first robotic anastomosis (n=7) was significantly longer than the second (n = 11) (56.3 vs. 38.3; p = .03). The first robotic anastomosis had a negative slope (-8.5). Interestingly, both the second robotic end-to-side anastomosis and the hand-sewn control had shallow positive slopes (1.5 and 2.6). The average of the robotic interrupted sutures (n = 11) was significantly longer than the hand-sewn (n = 23) (286 s vs. 70; p<.01). The average time for the first robotic interrupted anastomosis (n = 7) was significantly longer than the second (n = 4) (366.9 s vs. 144.5; p=0.008).

CONCLUSIONS:
Our results indicate that the learning curve for suturing robotic microanastomoses is short and encouraging. Similar performance to hand-sewn running sutures is possible robotically with minimal practice. Although the learning curve for the interrupted group was encouraging, we only reached similar results to hand-sewn in the very last robotic sutures. Overall, the use of robotics warrants further study for potential use in cerebrovascular bypass procedures.
221 Submaximal Angioplasty Alone Versus Stenting Plus Angioplasty for Symptomatic Intracranial Atherosclerotic Disease a Propensity Score Matched Comparative Study With Long Term Follow-Up
Authors: Baig Ammad , Aguirre Alexander Otilio , Donnelly Brianna M. , Kuo Cathleen , Kruk Marissa , Im Justin , Joseph Naomi , Palka Charles , Maini Aniket , Hashmi Eisa , Lim Jaims , Turner Ryan C. , Lai Rosalind , Raygor Kunal P. , Siddiqui Adnan Hussain , Levy Elad I. 
Published: March 2024

INTRODUCTION:
Symptomatic intracranial atherosclerotic disease (ICAD) remains an important cause of recurrent stroke and acute ischemic event. Although the high periprocedural risk of intracranial stenting from recent randomized studies has dampened enthusiasm for such interventions, submaximal angioplasty without stenting may represent a safer endovascular treatment option.

METHODS:
A prospectively maintained database was retrospectively searched for patients presenting with signs and symptoms of acute ischemic stroke or transient ischemic events. Patients subsequently underwent CT Stroke Study to confirm the diagnosis of symptomatic intracranial atherosclerotic disease. Patient baseline demographic characteristics, procedural details and post-procedure outcomes were recorded. A one-to-one matched propensity score analysis was performed to adjust for treatment selection bias using the nearest-neighbor matching technique without replacement for covariates (baseline comorbidities, previous stroke or TIA, antiplatelet use, anticoagulant use, and baseline percent diameter stenosis). Mann-Whitney U test was performed to compare the procedural parameters and the clinical outcomes between groups.

RESULTS:
We included 218 patients (Submaximal angioplasty:97 [97 after PSM]; Stenting plus angioplasty:121 [97 after PSM]). After PSM, no difference was seen between the two groups in terms of comorbidities, and initial stroke severity. Submaximal angioplasty group had significantly lower incidence of stroke/TIA secondary to restenosis on follow-up (6.2% vs. 20.6% (OR = 0.87; P = 0.003)), and longer length of follow-up after discharge (4.17 years vs. 2.88 years (OR = 0.98; P = 0.03)) when compared to stenting plus angioplasty group. Both groups had similar rates of intra- (2.1% vs. 6.2% (OR = 0.96; P = 0.15)) and post-procedural complications rates (6.2% vs. 11.3% (OR = 0.95; P = 0.21)).

CONCLUSIONS:
Submaximal angioplasty alone results in better long-term clinical outcomes in terms of stroke/TIA when compared with stenting and angioplasty for symptomatic intracranial atherosclerotic disease, and represents a potentially promising intervention.
223 An Artificial Intelligence Framework for Brain Tumor Delineation in Intraoperative Ultrasound
Authors: Dorent Reuben , Torio Erickson , Haouchine Nazim , Juvekar Parikshit , Frisken Sarah , Golby Alexandra J. , Kapur Tina , Wells William 
Published: March 2024

INTRODUCTION:
Automated delineation of gliomas in intraoperative ultrasound (iUS) could provide timely information to surgeons. While artificial intelligence (AI) frameworks have shown promising results for delineating gliomas in preoperative MRI, automated delineation in iUS remains a challenging and open problem.

METHODS:
A deep learning algorithm was developed to automatically delineate gliomas in intraoperative ultrasound. Instead of using time-consuming manual delineations from experts, the algorithm was developed using MR-based automated delineations. First, a MR nnUnet was trained for delineating gliomas in 3D preoperative MRI using an annotated public dataset (N=1000; RSNA-ASNR-MICCAI-BraTS 2021). Then, this algorithm delineated gliomas in preoperative MRI of patients (N = 84) in whom pre-dural opening 3D iUS reconstructed from a tracked handheld 2D probe was also acquired. To obtain the MR-based delineations in iUS, preoperative MRI and iUS were aligned using NiftyReg. Finally, a 3D iUS nnUnet was trained using a random subset (N = 78) of this pseudo-annotated iUS dataset. The method was assessed on the remaining test set (N = 943 slices from 6 volumes), with a treating neurosurgeon delineating gliomas in 2D iUS only and then in 2D iUS and aligned MR slices to obtain gold-standard delineations.

RESULTS:
The median Dice scores of the nnUnet and the neurosurgeon were respectively 78.6% (IQ:15.5%) and 84.3% (IQ: 21.1%) against the gold-standard delineations. In this preliminary study, the network's performance was comparable to the neurosurgeon's (two paired one-sided tests, equivalence margin:5%, p<1e-5, N = 943), with rapid delineation (<10 second) of 3D iUS (95-216 slices) compared to neurogeons (32-93 minutes), making automated delineation practical during surgery.

CONCLUSIONS:
The results demonstrate the feasibility of using AI-based methods for automated delineation of brain tumors in iUS, which could improve surgical outcomes by providing real-time information to surgeons.