Publications by authors named "Gregory J Zipfel"

Background And Objectives: First-line therapy for most intracranial dural arteriovenous fistulas (dAVFs) is endovascular embolization, but some require microsurgical ligation due to limited endovascular accessibility, anticipated lower cure rates, or unacceptable risk profiles. We investigated the most common surgically treated dAVF locations and the approaches and outcomes of each.

Methods: The Consortium for Dural Arteriovenous Fistula Outcomes Research database was retrospectively reviewed.

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  • Researchers are developing better animal models for aneurysmal subarachnoid hemorrhage (SAH) to study the condition more effectively, as current models fail to mimic the long-term cognitive issues experienced by patients.
  • A new mouse model has been created that reliably produces significant long-term cognitive deficits by modifying a previous injection method, allowing for consistent results.
  • This mouse model effectively mirrors key characteristics of SAH in humans, making it a valuable tool for exploring SAH-related brain injury and potential treatments for cognitive impairments.
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  • The study investigates whether isoflurane conditioning provides neuroprotection against peripheral nerve injuries in a rodent model.
  • Adult male Lewis rats were divided into four groups based on their exposure to isoflurane after sciatic nerve injury, with some receiving multiple exposure sessions over consecutive days.
  • Results showed significant improvements in nerve function and structure (like increased axons and better muscle performance) in groups that underwent 3- and 6-day isoflurane conditioning, suggesting potential therapeutic benefits for nerve repair.
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Objective: The number of cerebrovascular (CV) surgeons has grown with the rise of endovascular neurosurgery. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased. With increasing numbers of CV neurosurgeons in the US workforce, the authors analyzed associated changes in National Institutes of Health (NIH) and Neurosurgery Research and Education Foundation (NREF) funding trends for CV surgeons over time.

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  • This study evaluated the safety and effectiveness of using disulfiram and copper (DSF/Cu) alongside radiation therapy (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) patients.
  • It involved administering standard RT and TMZ with DSF and Cu, followed by adjuvant treatment, while tracking drug concentrations in the body.
  • Although the maximum tolerated dose of DSF was 375 mg/d, the treatment showed limited overall success, except for promising results in BRAF-mutant patients, suggesting the need for further research.
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Background: Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH.

Methods: In this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation.

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  • Developing accurate animal models of aneurysmal subarachnoid hemorrhage (SAH) is essential for understanding its effects and potential treatments, as current models often fail to mimic the real-life conditions faced by human patients.
  • This study introduces a standardized mouse model that replicates significant long-term neurobehavioral deficits seen in SAH, specifically through a modified injection technique in the mouse brain.
  • The new model allows researchers to better explore the underlying mechanisms of SAH and discover new therapeutic options aimed at improving cognitive outcomes for patients following this condition.
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Purpose: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines.

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Introduction: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated.

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Background: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients.

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Objective: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood.

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  • Vestibular schwannomas (VS) are non-cancerous tumors that can cause significant health issues, but how their diversity and surrounding environment affect their development is not well understood.
  • The study utilized single-cell RNA sequencing (scRNA-seq) and other genomic techniques on various VS samples, discovering different types of cells involved in the tumor environment and revealing a link between certain Schwann cells and inflammation often seen in nerve injuries.
  • Findings suggest that these Injury-like Schwann cells may promote tumor growth by attracting immune cells through a specific signaling pathway, highlighting potential targets for future therapies.
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Background: Intracranial aneurysms of the middle cerebral artery can be treated using several open surgical and endovascular approaches. Given the growing evidence of clinical equipoise between these various treatment strategies, there is a need to assess the costs associated with each.

Methods: Cost of aneurysm treatment was divided into two categories for comparison.

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  • A study analyzed a large cohort of patients with dural arteriovenous fistulas (dAVFs) presenting cognitive impairment, called dAVFs-CI, to understand their characteristics compared to those without cognitive issues.
  • Findings showed that venous hypertension and sinus stenosis were common in dAVFs-CI, with these patients having more arterial feeders and draining veins, making their condition more severe.
  • Closing the dAVF may help improve symptoms in some cases, highlighting the importance of timely diagnosis and treatment.*
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Aneurysmal subarachnoid hemorrhage (SAH) carries significant mortality and morbidity, with nearly half of SAH survivors having major cognitive dysfunction that impairs their functional status, emotional health, and quality of life. Apart from the initial hemorrhage severity, secondary brain injury due to early brain injury and delayed cerebral ischemia plays a leading role in patient outcome after SAH. While many strategies to combat secondary brain injury have been developed in preclinical studies and tested in late phase clinical trials, only one (nimodipine) has proven efficacious for improving long-term functional outcome.

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The human cerebrovascular system is responsible for maintaining neural function through oxygenation, nutrient supply, filtration of toxins, and additional specialized tasks. While the cerebrovascular system has resilience imparted by elaborate redundant collateral circulation from supportive tertiary structures, it is not infallible, and is susceptible to developing structural vascular abnormalities. The causes of this class of structural cerebrovascular diseases can be broadly categorized as 1) intrinsic developmental diseases resulting from genetic or other underlying aberrations (arteriovenous malformations and cavernous malformations) or 2) extrinsic acquired diseases that cause compensatory mechanisms to drive vascular remodeling (aneurysms and arteriovenous fistulae).

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  • * This study aimed to investigate the neurovascular protective effects of propofol, a commonly used intravenous anesthetic, in a mouse model of SAH.
  • * The findings revealed that propofol did not protect against large artery vasospasm or sensory-motor deficits following SAH, suggesting that different anesthetic agents have varying levels of efficacy in protecting against DCI.
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Cerebral autoregulation impairment is a critical aspect of subarachnoid hemorrhage (SAH)-induced secondary brain injury and is also shown to be an independent predictor of delayed cerebral ischemia (DCI) and poor neurologic outcomes. Interestingly, intraoperative hemodynamic and ventilatory parameters were shown to influence patient outcomes after SAH. The aim of the current study was to evaluate the association of intraoperative hypotension and hypocapnia with the occurrence of angiographic vasospasm, DCI, and neurologic outcomes at discharge.

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A benchmark of success for the neurosurgeon-scientist includes obtaining individual research funding from the National Institutes of Health. Successful roadmaps to this goal highlight diversity, individual commitment and resiliency, innovative research goals, intentional mentoring, protected research time, and financial support. We must equip neurosurgery residents to surmount obstacles such as long periods of training, gaps in research productivity, and limited protected time for research to ensure successful transition to independent research careers.

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A benchmark of success for the neurosurgeon-scientist includes obtaining individual research funding from the National Institutes of Health. Successful roadmaps to this goal highlight individual commitment and resiliency, innovative research goals, intentional mentoring, protected research time, and financial support. Neurosurgery residents must carefully plan their training career to surmount obstacles such as long clinical training period, gaps in research productivity during clinical training, and limited protected time for research to ensure successful transition to independent research careers.

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Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH.

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Delayed cerebral ischemia (DCI) is the largest treatable cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-kB), a transcription factor known to function as a pivotal mediator of inflammation, is upregulated in SAH and is pathologically associated with vasospasm. We previously showed that a brief exposure to isoflurane, an inhalational anesthetic, provided multifaceted protection against DCI after SAH.

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 A low subfrontal dural opening technique that limits brain manipulation was assessed in patients who underwent frontotemporal approaches for anterior fossa lesions.  A retrospective review was performed for cases using a low subfrontal dural opening including characterization of demographics, lesion size and location, neurological and ophthalmological assessments, clinical course, and imaging findings.  A low subfrontal dural opening was performed in 23 patients (17F, 6M), median age of 53 years (range 23-81) with a median follow-up duration of 21.

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Background: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes.

Methods: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed.

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