Gregory J. Zipfel

Gregory J. Zipfel
Washington University in St. Louis | WUSTL , Wash U · Department of Neurosurgery

MD

About

320
Publications
22,411
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11,162
Citations
Citations since 2016
130 Research Items
6364 Citations
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201620172018201920202021202202004006008001,000
Introduction
I strive to provide leading-edge surgical care to my patients, while also assuring that they and their families feel supported and individually cared for throughout. Our Research Focus: - Examine effects of amyloid-β on cerebral arteriole function & assessing its contribution to brain injury, Cerebral Amyloid Angiopathy, and Alzheimer’s Disease. - Explore mechanisms that underlie vasospasm and cognitive deficits following aneurysmal SAH. visit our lab website: zipfellab.com

Publications

Publications (320)
Article
The central nervous system (CNS) antigen-presenting cell (APC) that primes anti-tumor CD8+ T-cell responses remains undefined. Elsewhere in the body, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDC localize to the choroid plexus and dura. Thus, whether the cDC1 play a...
Preprint
Full-text available
Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to the pathogenesis of these tumors remains poorly understood. We performed scRNA-seq on 15 VS samples, with paired scATAC-seq in six samples. We identified diverse Schwann ce...
Article
Objective: For patients with surgically accessible solitary metastases or oligometastatic disease, treatment often involves resection followed by postoperative stereotactic radiosurgery (SRS). This strategy has several potential drawbacks, including irregular target delineation for SRS and potential tumor "seeding" away from the resection cavity d...
Article
Background: An increase in sirtuin 1 (SIRT1) reportedly attenuates early brain injury, delayed cerebral ischemia, and short-term neurologic deficits in rodent models of subarachnoid hemorrhage (SAH). This study investigates the effect of resveratrol, a SIRT1 activator, on long-term functional recovery in a clinically relevant rat model of SAH. Me...
Article
Objective The role of hemorrhage volume in risk of vasospasm, delayed cerebral ischemia (DCI) and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH) is well-established. However, the relative contribution of blood within individual compartments is unclear. We present an automated technique for measuring not only total but also volumes of...
Article
Background Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natura...
Article
Objective To identify factors, including the use of intraoperative MRI (iMRI), impacting overall survival (OS) and progression-free survival (PFS) after resections of newly diagnosed intracranial grade II ependymomas performed across 4 different institutions. Methods Analyses of a multicenter mixed retrospective/prospective database assessed the i...
Article
Full-text available
Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) an...
Conference Paper
Introduction Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) have a high risk of rupture. The most important determinant of symptoms and risk of hemorrhage is the pattern of venous drainage. The absence of major venous sinuses in the anterior cranial fossa leads to drainage through delicate small cortical veins that can easily bleed...
Article
Full-text available
Background Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples. Methods Single-cell RNA sequencing of seven non-tum...
Article
BACKGROUND Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quan...
Article
Full-text available
Objective To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). Methods We performed a systematic review and international individual patient-data pooled analysis in patients...
Article
Introduction A low subfrontal dural opening technique that limits brain manipulation was assessed in patients who underwent frontotemporal approaches for anterior fossa lesions. Methods A retrospective review was performed for cases using a low subfrontal dural opening including characterization of demographics, lesion size and location, neurologic...
Article
Functional connectivity (FC) is a sensitive metric that provides a readout of whole cortex coordinate neural activity in a mouse model. We examine the impact of experimental SAH modeled through endovascular perforation, and the effectiveness of subsequent treatment on FC, through three key questions: 1) Does the endovascular perforation model of SA...
Article
Full-text available
Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-β (Aβ) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro an...
Presentation
Tau hyperphosphorylation at Threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer disease (AD). However, it remains unclear whether pT217 could be modified in other tauopathies. Using immunoprecipitation and mass spectrometry, we compared CSF T2...
Article
Background Inhalational anesthetics were associated with reduced incidence of angiographic vasospasm and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). Whether intravenous anesthetics provide similar level of protection is not known. Methods Anesthetic data were collected retrospectively for patients wit...
Article
Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic pr...
Article
Full-text available
Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to w...
Preprint
The central nervous system (CNS) antigen presenting cell (APC) which primes anti-tumor CD8 ⁺ T cell responses remains undefined. Elsewhere, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain cDC1 are rare; cDC localize to choroid plexus and dura. Using preclinical glioblastoma models and cDC1-deficient mice, we...
Article
OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, nat...
Article
OBJECTIVE Brain arteriovenous malformations (AVMs) carry a risk of rupture and subsequent morbidity or mortality unless fully treated. AVMs in pediatric patients are known to occasionally recur after obliteration. The objective of this study was to characterize the risk of AVM recurrence following angiographically confirmed obliteration in children...
Article
OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are often treated with endovascular therapy, but occasionally a multimodality approach including surgery and/or radiosurgery is utilized. Recurrence after an initial angiographic cure has been reported, with estimated rates ranging from 2% to 14.3%, but few risk factors have been identified. Th...
Article
OBJECTIVE Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD. METHODS The authors conducted an analysi...
Article
OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intrac...
Article
OBJECTIVE The risk-to-benefit profile of treating an unruptured high-grade dural arteriovenous fistula (dAVF) is not clearly defined. The aim of this multicenter retrospective cohort study was to compare the outcomes of different interventions with observation for unruptured high-grade dAVFs. METHODS The authors retrospectively reviewed dAVF patie...
Article
Background and Purpose Dural arteriovenous fistulae can present with hemorrhage, but there remains a paucity of data regarding subsequent outcomes. We sought to use the CONDOR (Consortium for Dural Arteriovenous Fistula Outcomes Research), a multi-institutional registry, to characterize the morbidity and mortality of dural arteriovenous fistula–rel...
Preprint
Recent investigation of the meninges, specifically the dura layer, has highlighted its importance in CNS immune surveillance beyond a purely structural role. However, most of our understanding of the meninges stems from the use of pre-clinical models rather than human samples. In this study, we use single cell RNA-sequencing to perform the first ch...
Article
Full-text available
Objective Tau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer’s disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, C...
Article
Background and purpose: Acute ischemic stroke has increasingly become a procedural disease following the demonstrated benefit of mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO) on clinical outcomes and tissue salvage in randomized trials. Given these data and anecdotal experience of decreased numbers of decompressive hemicr...
Article
Full-text available
Numerous studies have demonstrated the ability of isoflurane conditioning to provide multifaceted protection against aneurysmal subarachnoid hemorrhage (SAH)-associated delayed cerebral ischemia (DCI); however, preclinical studies have not yet examined whether other commonly used inhalational anesthetics in neurological patients such as sevoflurane...
Article
Full-text available
Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage....
Article
OBJECTIVE The Neurosurgery Research and Education Foundation (NREF) provides research support for in-training and early career neurosurgeon-scientists. To define the impact of this funding, the authors assessed the success of NREF awardees in obtaining subsequent National Institutes of Health (NIH) funding. METHODS NREF in-training (Research Fello...
Article
Full-text available
We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. T...
Article
Full-text available
Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology...
Article
Background The demand of thrombectomy treatment for acute ischemic stroke increased dramatically in the United States (US) following the publication of five pivotal trials in 2015. The impact of call burden on career satisfaction and burnout in neurointerventionalists has not been explored. Methods A qualitative approach was chosen to obtain rich,...
Article
Introduction: Dural artertiovenous fistulae (dAVF) are rare causes of secondary intracranial hemorrhage (ICH) and there remains a paucity of knowledge regarding their natural history. To date our knowledge comes from small case series. CONDOR, (Consortium for Dural Arteriovenous Fistula Outcomes Research), a large multi-institutional retrospective...
Article
Background Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance. Objective To carry out a multicenter study to determine the predictors of complications, obliteration, and functi...
Article
The ε4 allele of the apolipoprotein E ( APOE ) gene is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) and greatly influences the development of amyloid-β (Aβ) pathology. Our current study investigated the potential therapeutic effects of the anti-human APOE antibody HAE-4, which selectively recognizes human APOE that is c...
Article
Background and Purpose Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accept...
Article
BACKGROUND Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial. OBJECTIVE To compare the outcomes of observation versus intervention for low-grade dAVFs. METHODS We retrospectively reviewed dAVF patients from institutions pa...
Article
Purpose Moyamoya disease and syndrome are progressive steno-occlusive cerebrovascular diseases that manifest clinically with ischemic episodes. There is evidence for the use of electroencephalography (EEG) in preoperative and long-term postoperative evaluation of these patients, as well as in the intraoperative period to monitor for changes correla...
Article
Full-text available
Delayed cerebral ischemia (DCI) is identified as one of the significant contributors to poor patient outcome after aneurysmal subarachnoid hemorrhage (SAH). We previously reported that a supratherapeutic dose of isoflurane conditioning (2%) provided robust protection against SAH-induced DCI. The aim of our current study is to compare the efficacy o...
Article
Background and purpose Vasospasm and delayed cerebral ischemia (DCI) contribute significantly to the morbidity/mortality associated with aneurysmal subarachnoid hemorrhage (SAH). While considerable research effort has focused on preventing or reversing vasospasm, SAH-induced brain injury occurs in response to a multitude of concomitantly acting pat...
Article
BACKGROUND Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative MRI (iMRI) in the resection of grade II gliomas. We assessed the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly-diagnosed grade II astrocytomas and oligodendrogliomas. METHODS Retrospe...
Article
BACKGROUND Although endoscopic transsphenoidal surgery (ETSS) is an established treatment for patients with nonfunctioning pituitary adenomas (NFPAs), data are limited regarding the rates and predictors of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS. OBJECTIVE To analyze the comprehensive changes in hormon...
Article
The antigen presenting cell that primes T cells in the central nervous system (CNS) remains unknown. Outside the CNS, the conventional dendritic cell 1 (cDC1) subset presents antigen to and primes CD8 T cells. However, the steady-state CNS parenchyma is relatively devoid of all dendritic cell subsets, including cDC1. cDC1 are required for anti-tumo...
Article
Background and purpose: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its re...
Article
Full-text available
Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning‐induced neurovascular protection after SAH. Methods and Results Ten‐ to 14‐week‐old male wild‐...
Article
Objective: Intraoperative MRI (iMRI) is used in the surgical treatment of glioblastoma, with uncertain effects on outcomes. The authors evaluated the impact of iMRI on extent of resection (EOR) and overall survival (OS) while controlling for other known and suspected predictors. Methods: A multicenter retrospective cohort of 640 adult patients w...
Article
Background: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been identified as an independent predictor of poor outcome in numerous studies. Objective: To investigate the potential protective role of inhalational anesthetics against angiographic vasospasm, DCI, and neurologic outcome in SAH patients. Methods:...
Article
BACKGROUND Intraoperative magnetic resonance imaging (iMRI) is a powerful tool for guiding brain tumor resections, provided that it accurately discerns residual tumor. OBJECTIVE To use histopathology to assess how reliably iMRI may discern additional tumor for a variety of tumor types, independent of the indications for iMRI. METHODS A multicente...
Article
Full-text available
PurposeEndoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to...
Conference Paper
Background Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) lacking cortical venous drainage (CVD) have a benign clinical course. However, there is no large study evaluating the safety/efficacy of current treatments and their impact over the natural history of no-CVD dAVFs. Methods We conducted an analysis of the re...
Article
Background: Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas. Objective: To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and o...
Article
Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VER i TAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We...
Article
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been associated with numerous pathophysiological sequelae, including large artery vasospasm and microvascular thrombosis. The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal-spati...
Article
Background and Purpose: Given the benign natural history of intracranial low-grade dural arteriovenous fistulas (dAVFs), their routine treatment remains controversial. The aim of this study is to compare the outcomes of low-grade dAVF treatment to conservative management. Methods: We performed a retrospective review of dAVF patients derived from 12...
Article
Objective: To assess the impact of intraoperative magnetic resonance imaging (iMRI), extent of resection (EOR), and other factors on overall survival (OS) and progression-free survival (PFS) for patients with newly diagnosed grade I gliomas. Methods: A multicenter database was queried to identify patients with grade I gliomas. Retrospective anal...
Article
Background Use of the radial artery as an access site for neurointerventional procedures is gaining popularity after several studies in interventional cardiology have demonstrated superior patient safety, decreased length of stay, and patient preference compared with femoral artery access. The transradial approach has yet to be characterized for in...
Article
Full-text available
Background and Purpose— Several angiographic factors of dural arteriovenous fistulas (dAVFs) are associated with aggressive presentation and poor natural history. We examined the association of magnetic resonance imaging T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) hyperintensity with aggressive presentation. Methods— A cohort of dAV...
Poster
Objective: Nontraumatic convexity subarachnoid haemorrhage (cSAH) in older people is an increasingly recognised presentation of cerebral amyloid angiopathy (CAA). Data on risks of future intracranial bleeding and ischaemia are needed to inform prognosis and management. We investigated the frequency, time-course and predictors of symptomatic intrace...
Article
OBJECTIVE Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several...
Article
INTRODUCTION The Common Data Elements (CDEs) initiative is a National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) effort to standardize naming, definitions, data coding, and data collection for observational studies and clinical trials in major neurological disorders. A working group of experts was establishe...
Article
Introduction: The Common Data Elements (CDEs) initiative is a National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) effort to standardize naming, definitions, data coding, and data collection for observational studies and clinical trials in major neurological disorders. A working group of experts was establis...
Article
2033 Background: Disulfiram (DSF) has shown promising activity against glioblastoma in preclinical studies and is more effective when combined with copper (Cu). Our previous phase I study established the maximum tolerated dose (MTD) of DSF when combined with adjuvant temozolomide (TMZ). This phase I/II study aims to establish the MTD when disulfira...
Article
Object: The Wishbone device is designed to enable surgeons to quickly and accurately localize the cranial midline. It is intended to be of particular use when localizing the burr-hole site during posterior VPS surgery. Methods: The Wishbone is a simple mechanical device with two adjustable caliper arms that reversibly attach to a patient's left...
Article
OBJECTIVE Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) may result in focal neurological deficits and cerebral infarction, believed to result from critical regional rather than global impairments in cerebral blood flow (CBF). However, the burden of such regional hypoperfusion has not been evaluated by gold-standard voxel-by-vo...
Article
Over the past decade substantial advances in diagnostic imaging, classification, and understanding the natural history of intracranial dural arteriovenous fistula (dAVF) have been made. Paralleling these improvements in patient evaluation and risk assessment have been considerable innovations and refinements in the microsurgical and endovascular te...