Posterior Interhemispheric Approach for Occlusion of a Galenic (Type 1) Tentorial Dural Arteriovenous Fistula: 2-Dimensional Operative Video.

Galenic dural arteriovenous fistulas account for 1 of the 6 types of tentorial dural arteriovenous fistulas (type I). These fistulas are located around the great cerebral vein of Galen, with dural arterial supply through the tentorial arteries of Bernasconi and Cassinari or other posterior fossa branches, such as the posterior meningeal artery. In this case, a man in his 60s presented with a headache and was found to have this high-risk lesion, which was Borden grade III and Cognard grade IV. The lesion persisted despite embolization through the middle meningeal artery. This video discusses the microsurgical management of this lesion through a torcular craniotomy and a posterior interhemispheric approach for clipping. Because this is a single case report, institutional review board approval was not needed. The patient consented to the procedure. Used with permission from Barrow Neurological Institute, Phoenix, Arizona. Images at 7:19 and 7:49 in Surgical Video are used with permission from Lawton, Michael T.; Sanchez-Mejia, Rene O.; Pham, Diep; Tan, Jeffrey; Halbach, Van V. Tentorial Dural Arteriovenous Fistulae: Operative Strategies and Microsurgical Results for Six Types. Operative Neurosurgery 62(3): 110-125, 2008.

Multicenter US clinical experience with the Scepter Mini balloon catheter.

INTRODUCTION: Distal navigability and imprecise delivery of embolic agents are two limitations encountered during liquid embolization of cerebrospinal lesions. The dual-lumen Scepter Mini balloon (SMB) microcatheter was introduced to overcome these conventional microcatheters' limitations with few small single-center reports suggesting favorable results. METHODS: A series of consecutive patients undergoing SMB-assisted endovascular embolization were extracted from prospectively maintained registries in seven North-American centers (November 2019 to September 2022). RESULTS: Fifty-four patients undergoing 55 embolization procedures utilizing SMB were included (median age 58.5; 48.1% females). Cranial dural arteriovenous fistula embolization was the most common indication (54.5%) followed by cranial arteriovenous malformation (27.3%). Staged/pre-operative embolization was done in 36.4% of cases; and 83.6% of procedures using Onyx-18. Most procedures utilized a transarterial approach (89.1%), and SMB-induced arterial-flow arrest concurrently with transvenous embolization was used in 10.9% of procedures. Femoral access/triaxial setups were utilized in the majority of procedures (65.5% and 60%, respectively). The median vessel diameter where the balloon was inflated of 1.8 mm, with a median of 1.5 cc of injected embolic material per procedure. Technical failures occurred in 5.5% of cases requiring aborting/replacement with other devices without clinical sequelae in any of the patients, with SMB-related procedural complications of 3.6% without clinical sequelae. Radiographic imaging follow-up was available in 76.9% of the patients (median follow-up 3.8 months), with complete occlusion (100%) or >50% occlusion in 92.5% of the cases, and unplanned retreatments in 1.8%. CONCLUSION: The SMB microcatheter is a useful new adjunctive device for balloon-assisted embolization of cerebrospinal lesions with a high technical success rate, favorable outcomes, and a reasonable safety profile.

Middle meningeal artery patency after surgical evacuation for chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) often requires surgical evacuation, but recurrence rates remain high. Middle meningeal artery (MMA) embolization (MMAE) has been proposed as an alternative or adjunct treatment. There is concern that prior surgery might limit patency, access, penetration, and efficacy of MMAE, such that some recent trials excluded patients with prior craniotomy. However, the impact of prior open surgery on MMA patency has not been studied. METHODS: A retrospective analysis was conducted on patients who underwent MMAE for cSDH (2019-2022), after prior surgical evacuation or not. MMA patency was assessed using a six-point grading scale. RESULTS: Of the 109 MMAEs (84 patients, median age 72 years, 20.2% females), 58.7% were upfront MMAEs, while 41.3% were after prior surgery (20 craniotomies, 25 burr holes). Median hematoma thickness was 14 mm and midline shift 3 mm. Hematoma thickness reduction, surgical rescue, and functional outcome did not differ between MMAE subgroups and were not affected by MMA patency or total area of craniotomy or burr-holes. MMA patency was reduced in the craniotomy group only, specifically in the distal portion of the anterior division (p = 0.005), and correlated with craniotomy area (p < 0.001). CONCLUSION: MMA remains relatively patent after burr-hole evacuation of cSDH, while craniotomy typically only affects the frontal-distal division. However, MMA patency, evacuation method, and total area do not affect outcomes. These findings support the use of MMAE regardless of prior surgery and may influence future trial inclusion/exclusion criteria. Further studies are needed to optimize the timing and techniques for MMAE in cSDH management.

Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. METHOD: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007-July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. RESULTS: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4-1.2, p = 0.18). CONCLUSIONS: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms.

Microsurgical Resection of Brainstem Cavernous Malformations in Older Adults: A Multicenter, 30-Year Experience.

BACKGROUND AND OBJECTIVES: Microsurgical resection is the only curative intervention for symptomatic brainstem cavernous malformations (BSCMs), but the management of these lesions in older adults (≥65 years) is not well described. This study sought to address this gap by examining the safety and efficacy of BSCM resection in a cohort of older adults. METHODS: Records of patients who underwent BSCM resection over a 30-year period were reviewed retrospectively. Baseline characteristics and outcomes were compared between older (≥65 years) and younger (<65 years) patients. RESULTS: Of 550 patients with BSCM who met inclusion criteria, 41 (7.5%) were older than 65 years. Midbrain (43.9% vs 26.1%) and medullary lesions (19.5% vs 13.6%) were more common in the older cohort than in the younger cohort (P = .01). Components of the Lawton BSCM grading system (ie, lesion size, crossing axial midpoint, developmental venous anomaly, and timing of hemorrhage) were not significantly different between cohorts (P ≥ .11). Mean (SD) Elixhauser comorbidity score was significantly higher in older patients (1.86 [1.06]) than in younger patients (0.66 [0.95]; P < .001). Older patients were significantly more likely than younger patients to have poor outcomes at final follow-up (28.9% vs 13.8%, P = .01; mean follow-up duration, 28.7 [39.1] months). However, regarding relative neurological outcome (preoperative modified Rankin Scale to final modified Rankin Scale), rate of worsening was not significantly different between older and younger patients (23.7% vs 14.9%, P = .15). CONCLUSION: BSCMs can be safely resected in older patients, and when each patient's unique health status and life expectancy are taken into account, these patients can have outcomes similar to younger patients.

Endovascular biopsy in neurointerventional surgery: A systematic review.

INTRODUCTION: Endothelial cells (ECs) continuously line the cerebrovasculature. Molecular aberrations in the ECs are hallmarks and contributory factors to the development of cerebrovascular diseases, including intracranial aneurysms and arteriovenous malformations (AVMs). Endovascular biopsy has been introduced as a method to harvest ECs and obtain relevant biologic information. We aimed to summarize the literature on endovascular biopsy in neurointerventional surgery. METHODS: We conducted a comprehensive literature search in multiple databases, identifying eligible studies focusing on neurosurgical applications of endovascular biopsy. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The relevant information was collected, including study characteristics, biopsy techniques, and key findings. RESULTS: Nine studies met the inclusion criteria and were included. The studies involved the collection of ECs using various endovascular devices including coils, guide wires, different stents, and forceps. Endothelial-enrichment techniques, such fluorescence-activated cell sorting (FACS), collected ECs and facilitated downstream applications of bulk or single-cell RNA sequencing (scRNAseq). The studies provided insights into gene expression profiles and identified potential biomarkers associated with intracranial aneurysms. However, challenges were observed in obtaining an adequate number of ECs and identifying consistent biomarkers. CONCLUSION: Endovascular biopsy of endothelial cells (ECs) in cerebrovascular pathologies shows promise for gene expression profiling. However, many studies have been limited in sample size and underpowered to identify "signature genes" for aneurysm growth or rupture. Advancements in minimally invasive biopsy methods have potential to facilitate applications of precision medicine in the treatment of cerebrovascular disorders.

Microsurgical Resection of a Lateral Pontine Arteriovenous Malformation Masquerading as a Cavernous Malformation: 2-Dimensional Operative Video.

Although cavernous malformations (CMs) often demonstrate characteristic T2 heterogeneity and gadolinium enhancement, whereas arteriovenous malformations (AVMs) appear as tangles of T2 hypointense flow voids, small lesions in deep locations may have equivocal features on preoperative imaging.1-4 This video presents an unusual case of a lateral pontine AVM masquerading as a CM. The patient presented with sudden-onset headache, dizziness, double vision, and left facial numbness. Diagnostic imaging findings suggested a hemorrhagic left lateral pontine mass lesion, most consistent with brainstem CM. Resection through a left extended retrosigmoid craniotomy was recommended. Patient consent was obtained. During dissection, a prominent petrosal vein tributary was noted to be arterialized, which was concerning for AVM. Indocyanine green videoangiography (ICG-VA) was performed to confirm the diagnosis, and the intraoperative plan was dynamically adjusted in accordance with the principles of AVM resection. The small superficial feeding arteries were identified and disconnected, and the nidus was dissected circumferentially with the pial resection technique. After dearterialization, the draining petrosal vein was noted to darken, and repeat ICG-VA confirmed complete occlusion of the AVM without residual shunting. The patient recovered well, with no neurological deficits, and postoperative angiography confirmed complete resection of the Spetzler-Martin grade III AVM. Key learning points for this unusual case include the importance of dynamic interpretation of intraoperative findings, openness to alterations of the surgical plan when integrating new diagnostic information, and the integration of ICG-VA as a critical tool for differentiating CMs and AVMs during microsurgical resection. Images in Surgical Video © 2024 Barrow Neurological Institute. Used with permission.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

Readability of cerebrovascular diseases online educational material from major cerebrovascular organizations.

INTRODUCTION: The internet is an essential resource for patients and their loved ones to understand their medical conditions, and professional medical organizations have taken great strides to develop educational material targeting patients. The average American reads at a seventh to eighth grade reading level, hence it is important to understand the readability of this medical information to ensure patients comprehend what is being presented. METHODS: In January 2023, online patient education material was downloaded from major cerebrovascular healthcare organizations and assessed using eight assessments, including Bormuth Cloze Mean, Bormuth Grade Placement, Coleman-Liau (grade levels), Coleman-Liau (predictive cloze scores), Flesch Reading Ease (FRE), and Fry. RESULTS: A total of 32 files were extracted from six organizations and analyzed across 15 readability measures. None of the organizations met the federal government guidelines for grade-level readability. This held constant across all measured tests. Two organizations had above a postgraduate level. The FRE graphs do not identify any organizations with material below a ninth grade reading level, while the American Association of Neurological Surgeons (AANS) and the Society of Interventional Radiology (SIR) have a postgraduate readability level. The Fry graphs show similar results, with AANS/CNS Cerebrovascular Section, Society of NeuroInterventional Surgery (SNIS), SIR, and AANS having college-level readability. The lowest readability across all measures is only at an early seventh grade reading level. CONCLUSIONS: Current health literacy content for cerebrovascular patients is far above the recommended readability level. We provide straightforward suggestions for how major professional organizations should improve their informational material on cerebrovascular diseases to improve patient understanding.

Utilization and reimbursement of diagnostic cerebral angiograms: A Medicare trends analysis from 2013 to 2020.

INTRODUCTION: Increasing life expectancy has caused growing concern about maintaining viable neurointerventional practices due to altered Medicare payment structures. This study analyzes the financial trends of three common diagnostic tests for cerebrovascular disease: cerebral digital subtraction angiography (DSA), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). METHODS: Medicare Part B National Summary Data files from 2013 to 2020 were queried by Current Procedural Terminology (CPT) codes for DSA (36221-36228), CTA (70496, 70498), and MRA (70544-70547, 70549). Inflation-adjusted charges and reimbursement were calculated using the U.S. City Average Consumer Price Index for Medical Services. Regression analysis was performed on charges, reimbursement, and volume. RESULTS: A total of 1,519,245 diagnostic procedures were conducted between 2013 and 2020 (782,370 angiograms, 246,603 CTAs, and 490,272 MRAs). A total of $41.005 million was reimbursed by Medicare in 2020 for these diagnostic procedures. The annual percent change in volume for all procedures was -2.90%. From 2013 to 2020, inflation-adjusted: Medicare total physician reimbursement decreased for cerebral angiograms (-4.12%, p = 0.007), CTAs (-2.77%, p = 0.458), and MRAs (-9.06%, p < 0.001). Procedural volume billed to Medicare decreased for cerebral angiograms (-4.63%, p = 0.007) and MRAs (-2.94%, p = 0.0.81) and increased for CTAs (+3.15%, p = 0.004). The greatest increase in Medicare reimbursement (+66.75%) came from CPT code 36224, "place catheter carotid artery", and the greatest decrease in Medicare reimbursement (-8.66%) came from CPT code 36226, "place catheter vertebral artery." CONCLUSIONS: This study provides an analysis of Medicare reimbursement trends for routine cerebrovascular angiogram techniques. The findings highlight a decline in Medicare reimbursements for neurointerventionalists.

General Versus Nongeneral Anesthesia for Middle Meningeal Artery Embolization for Chronic Subdural Hematomas: Multicenter Propensity Score Matched Study.

BACKGROUND AND OBJECTIVES: The choice of anesthesia type (general anesthesia [GA] vs nongeneral anesthesia [non-GA]) in middle meningeal artery embolization (MMAE) procedures for chronic subdural hematomas (cSDH) differs between institutions and left to care team discretion given lack of standard guidelines. We compare the outcomes of GA vs non-GA in MMAE. METHODS: Consecutive patients receiving MMAE for cSDH at 14 North American centers (2018-2023) were included. Clinical, cSDH characteristics, and technical/clinical outcomes were compared between the GA/non-GA groups. Using propensity score matching (PSM), patients were matched controlling for age, baseline modified Rankin Scale, concurrent/prior surgery, hematoma thickness/midline shift, and baseline antiplatelet/anticoagulation. The primary end points included surgical rescue and radiographic success rates (≥50% reduction in maximum hematoma thickness with minimum 2 weeks of imaging). Secondary end points included technical feasibility, procedural complications, and functional outcomes. RESULTS: Seven hundred seventy-eight patients (median age 73 years, 73.2% male patients) underwent 956 MMAE procedures, 667 (70.4%) were non-GA and 280 were GA (29.6%). After running 1:3 PSM algorithm, this resulted in 153 and 296 in the GA and non-GA groups, respectively. There were no baseline/procedural differences between the groups except radial access more significantly used in the non-GA group (P = .001). There was no difference between the groups in procedural technical feasibility, complications rate, length of stay, surgical rescue rates, or favorable functional outcome at the last follow-up. Subsequent 1:1 sensitivity PSM retained the same results. Bilateral MMAE procedures were more performed under non-GA group (75.8% vs 67.2%; P = .01); no differences were noted in clinical/radiographic outcomes between bilateral vs unilateral MMAE, except for longer procedure duration in the bilateral group (median 73 minutes [IQR 48.3-100] vs 54 minutes [39-75]; P < .0001). Another PSM analysis comparing GA vs non-GA in patients undergoing stand-alone MMAE retained similar associations. CONCLUSION: We found no significant differences in radiological improvement/clinical outcomes between GA and non-GA for MMAE.

Mandibular Fossa Approach to Petroclival and Anterior Pontine Lesions.

Objective To describe the anatomy related to a novel approach to the petroclival region through the mandibular fossa for the treatment of petroclival and anterior pontine lesions. Design Five dry skulls were examined for surgical approach. Three adult cadaveric heads underwent bilateral dissection. One cadaveric head was evaluated with computed tomography after dissection. Setting This study was performed in an academic medical center. Participants Neurosurgical anatomy researchers performed this study using dry skulls and cadaveric heads. Main Outcome Measurements This was a proof-of-concept anatomical study. Results The mandibular fossa approach uses a vertical preauricular incision above the facial nerve branches. Removal of the temporomandibular joint exposes the mandibular fossa. The anterior boundary is the mandibular nerve at the foramen ovale, and the posterior boundary is the jugular foramen. The chorda tympani, eustachian tube, and tensor tympani muscle are sectioned. The carotid artery is transposed out of the petrous canal, and a petrosectomy is performed from Meckel's cave to the foramen magnum and anterior occipital condyle. Dural opening exposes the anterior pons, vertebrobasilar junction, bilateral vertebral arteries, and the ipsilateral anterior and posterior inferior cerebellar arteries. At completion, the temporomandibular joint is reconstructed with a prosthetic joint utilizing a second incision along the mandible. Conclusions The mandibular fossa approach is a new trajectory to the petroclival region and the anterior pons. It combines the more anterior angle of endoscopic approaches along with the enhanced control of open approaches. Further study is necessary before this approach is used clinically.

Anatomic Feasibility of a Superficial Temporal Artery to Distal Anterior Cerebral Artery Bypass With a Parietal Branch Interposition Graft: The Superficial Temporal Artery Telescope Bypass.

BACKGROUND AND OBJECTIVES: Revascularizing the postcommunicating segment of the anterior cerebral artery (ACA) using extracranial donor sites requires long interposition grafts. The superficial temporal artery (STA) is frequently used for extracranial-intracranial ACA revascularization. However, the length of either STA branch is not sufficient to reach the ACA with a proper caliber match, so an interposition graft is required. The aim of this study was to evaluate a bypass that uses the 2 main branches of the STA to reach the A3 (pericallosal) segment of the ACA. METHODS: The frontal and parietal branches of the STA were dissected from 10 cadaveric specimens. The middle internal frontal artery (MIFA) was exposed through an anterior interhemispheric approach. An interposition graft technique was applied using the parietal branch of the STA (pSTA) to connect the frontal branch of the STA (fSTA) with the MIFA. The bypass code is fSTA (E-Ec) pSTA + pSTA (E-Sc) MIFA. Measurements of length and caliber were taken at the anastomotic sites for the distal branches of the STA and the MIFA. RESULTS: The mean (SD) diameter of the MIFA measured 1.4 (0.2) mm, similar to the calibers of the frontal and parietal branches of the STA. The mean (SD) length of the end-to-side STA-MIFA bypass was 145.5 (7.4) mm, and the mean (SD) length of the donor-graft construct measured 204.2 (27.9) mm. This bypass design resulted in a surplus donor graft length of 38%. CONCLUSION: Using the pSTA as an interposition graft proved to be a successful technique for creating an STA-MIFA bypass, yielding excess donor graft length that facilitated an unstrained bypass construct. This approach offers several advantages, including a single skin incision, ample graft length, caliber compatibility, and a straightforward technical execution.

Fenestrated Aneurysm Clip Trigeminal Decompression after CyberKnife Treatment Failure.

Objective This article describes a novel technique for trigeminal nerve decompression in the setting of refractory trigeminal neuralgia (TN). Design Technical note with an illustrative case example and operative video. Setting Outpatient, inpatient, and operating room of a quaternary neurosurgical referral center. Participant A woman in her early 70s who had previously undergone linear accelerator-based stereotactic radiotherapy (i.e., CyberKnife) and achieved 2 years of partial pain relief. However, facial pain, numbness, and parasympathetic dysfunction returned and became unbearable. Main Outcome Measure Durable relief of TN. Results Microvascular decompression was recommended for refractory TN. Intraoperatively, the trigeminal nerve was markedly attenuated from previous irradiation, with the superior cerebellar artery (SCA) loop embedded in the nerve at its root entry zone. The arterial loop was mobilized into a new position superior to the nerve, thus liberating it from the impingement. The tentorium was incised, and a fenestrated aneurysm clip was positioned such that the SCA loop was transmitted via the fenestration. The clip was applied across the tentorium, thus suspending the artery in a kink-free orientation that made no contact with the nerve. Conclusion This procedure provided excellent neurovascular decompression without placing mechanical strain on the nerve, relieving the patient's persistent postirradiation TN. The technique could have broader applications for other challenging or atypical microvascular decompression procedures.

Comprehensive neurosurgical treatment of right occipital arteriovenous malformation with advanced angiographic techniques.

/Summary. A 39-year-old female with a notable medical history of smoking and a familial predisposition to unruptured aneurysms presented with clinical symptoms of intermittent right-sided headaches, flashes of light, and pulsatile tinnitus in the right ear. Diagnostic evaluations, including advanced angiographic techniques, identified a right occipital arteriovenous malformation (AVM). The angiogram revealed significant venous flow voids, emphasizing the need for a comprehensive treatment approach. The Spetzler-Martin grading system classified the AVM as Grade 2, indicating a moderate risk profile. A strategic decision was made to undergo partial embolization of two primary arterial feeders from the right posterior cerebral artery (PCA). Subsequent post-embolization angiograms confirmed a marked reduction in arteriovenous shunting, validating the efficacy of the intervention. The surgical approach encompassed an occipital craniotomy, meticulous subarachnoid dissection, and intraoperative angiography to ensure complete resection. Post-operative assessments showcased a successful and complete AVM resection. The patient experienced a brief, transient headache post-surgery, which resolved on its own. She was discharged on the third post-operative day and has since reintegrated into her professional life. However, she reported a minor visual field deficit, which, while noticeable, did not impede her daily activities. This case underscores the importance of a holistic, patient-centric approach in managing AVMs [1-3]. It challenges the conventional wisdom from the ARUBA trial, advocating for a more nuanced, individualized treatment paradigm, especially for young patients with low-grade AVMs [4].

Early Treatment of Ruptured Cerebral Arteriovenous Malformations: Analysis of Neurological Outcomes and Health Care Costs.

BACKGROUND: The timing of surgical resection is controversial when managing ruptured arteriovenous malformations (AVMs) and varies considerably among centers. OBJECTIVE: To retrospectively analyze clinical outcomes and hospital costs associated with delayed treatment in a ruptured cerebral AVM patient cohort. METHODS: Patients undergoing surgical treatment for a ruptured cerebral AVM (January 1, 2015-December 31, 2020) were retrospectively analyzed. Patients who underwent emergent treatment of a ruptured AVM because of acute herniation were excluded, as were those treated >180 days after rupture. Patients were stratified by the timing of surgical intervention relative to AVM rupture into early (postbleed days 1-20) and delayed (postbleed days 21-180) treatment cohorts. RESULTS: Eighty-seven patients were identified. The early treatment cohort comprised 75 (86%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 5 (5) days in the early cohort and 73 (60) days in the delayed cohort ( P < .001). The cohorts did not differ with respect to patient demographics, AVM size, Spetzler-Martin grade, frequency of preoperative embolization, or severity of clinical presentation ( P ≥ .15). Follow-up neurological status was equivalent between the cohorts ( P = .65). The associated mean health care costs were higher in the delayed treatment cohort ($241 597 [$99 363]) than in the early treatment cohort ($133 989 [$110 947]) ( P = .02). After adjustment for length of stay, each day of delayed treatment increased cost by a mean of $2465 (95% CI = $967-$3964, P = .002). CONCLUSION: Early treatment of ruptured AVMs was associated with significantly lower health care costs than delayed treatment, but surgical and neurological outcomes were equivalent.

Development of a rabbit human glioblastoma model for testing of endovascular selective intra-arterial infusion (ESIA) of novel stem cell-based therapeutics.

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24). METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on magnetic resonance imaging, histologic, and immunohistochemistry analysis. Selective microcatheter infusion of MSC-D24 was performed via the ipsilateral internal carotid artery to assess model utility and the efficacy and safety of this approach. RESULTS: Twenty-five rabbits were implanted (18 with U87, 2 MDA-GSC-17, and 5 MDA-GSC-8-11). Tumors formed in 68% of rabbits (77.8% for U87, 50.0% for MDA-GSC-17, and 40.0% for MDA-GSC-8-11). On MRI, the tumors were hyperintense on T2-weighted image with variable enhancement (evidence of blood brain barrier breakdown). Histologically, tumors showed phenotypic traits of human GBM including varying levels of vascularity. ESIA infusion into the distal internal carotid artery of 2 ml of MSCs-D24 (107 cells) was safe in the model. Examination of post infusion specimens documented that MSCs-D24 homed to the implanted tumor at 24 hours. CONCLUSIONS: The intracranial immunosuppressed rabbit human GBM model allows testing of ESIA infusion of novel therapeutics (eg, MSC-D24) in a clinically relevant fashion.