240 results on '"Ethan A. Winkler"'
Search Results
2. Sex‐Dependent Manifestations of Intracranial Aneurysms
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Thomas Wälchli, Martin Ndengera, Paul E. Constanthin, Jeroen Bisschop, Sandrine Morel, Oliver Gautschi, Moncef Berhouma, Aristotelis Kalyvas, Philippe P. Monnier, Ethan A. Winkler, Hans Kortman, Kartik Bhatia, Philipp Dammann, Max Jägersberg, Renato Gondar, Karl Schaller, Brenda R. Kwak, and Philippe Bijlenga
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biological sex ,cerebrovascular disease ,cerebrovascular surgery ,intracranial aneurysms ,stroke ,vascular neurology ,Neurology. Diseases of the nervous system ,RC346-429 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Intracranial aneurysms (IAs) are more common in women than in men; however, there is still limited knowledge on sex‐dependent differences regarding aneurysm location, multiplicity, rupture risk, risk factors, and histopathology. Methods This cross‐sectional, consecutive cohort study examined whether IAs differ in multiplicity, location, geometry, rupture risk, risk factors, and histology between sexes. Results We included 982 patients (714 women, 268 men) totaling 1484 IAs (1056 unruptured, 397 ruptured). A total of 363 patients (36.97%) had multiple IAs, the proportion of which was significantly higher in women. In women, the internal carotid artery (40.79%) was the most frequent location for IAs, whereas in men most were found along the anterior carotid artery territory (32.86%). Men were significantly more often diagnosed with ruptured aneurysms. Aneurysm geometry did not differ between sexes; however, ruptured aneurysms in men presented with a significantly larger neck diameter than unruptured ones. Regarding risk factors for aneurysm rupture, blood pressure control was more effective in women, whereas the effect of smoking status did not show clear sex‐dependent differences. Histologically, wall‐type classification analysis showed significantly more severe aneurysm wall types in men. Conclusion IA prevalence in women is significantly higher than in men. Women more often present with multiple IAs, whereas men were more often diagnosed with ruptured IAs. Sex‐specific differences in IA location were identified, whereas geometry of IAs did not differ between sexes. IAs in men showed a more severe histological wall type. Further research is needed to unravel the molecular mechanisms underlying these important sex‐dependent manifestations in IAs.
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- 2024
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3. Author Correction: Pericyte loss influences Alzheimer-like neurodegeneration in mice
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Abhay P. Sagare, Robert D. Bell, Zhen Zhao, Qingyi Ma, Ethan A. Winkler, Anita Ramanathan, and Berislav V. Zlokovic
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Science - Published
- 2023
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4. Assessing the Relationship between Surgical Timing and Postoperative Seizure Outcomes in Cavernoma-Related Epilepsy: A Single-Institution Retrospective Analysis of 63 Patients with a Review of the Literature
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Elsa Nico, Christopher O. Adereti, Ashia M. Hackett, Andrea Bianconi, Anant Naik, Adam T. Eberle, Pere J. Cifre Serra, Stefan W. Koester, Samuel L. Malnik, Brandon M. Fox, Joelle N. Hartke, Ethan A. Winkler, Joshua S. Catapano, and Michael T. Lawton
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antiepileptic drugs ,cavernoma ,cavernoma-related epilepsy ,cavernous angioma ,cavernous hemangioma ,cavernous malformation ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010–31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.
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- 2024
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5. Racial and Socioeconomic Status among a Patient Population Presenting with Aneurysmal Subarachnoid Hemorrhage versus Unruptured Intracranial Aneurysm: A Single-Center Study
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Ashia M. Hackett, Christopher O. Adereti, Ariel P. Walker, Elsa Nico, Lea Scherschinski, Emmajane G. Rhodenhiser, Adam T. Eberle, Anant Naik, Juan P. Giraldo, Joelle N. Hartke, Redi Rahmani, Ethan A. Winkler, Joshua S. Catapano, and Michael T. Lawton
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aneurysmal subarachnoid hemorrhage ,socioeconomic status ,unruptured intracranial aneurysm ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Racial and socioeconomic health disparities are well documented in the literature. This study examined patient demographics, including socioeconomic status (SES), among individuals presenting with aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (UIA) to identify factors associated with aSAH presentation. A retrospective assessment was conducted of all patients with aSAH and UIA who presented to a large-volume cerebrovascular center and underwent microsurgical treatment from January 2014 through July 2019. Race and ethnicity, insurance type, and SES data were collected for each patient. Comparative analysis of the aSAH and UIA groups was conducted. Logistic regression models were also employed to predict the likelihood of aSAH presentation based on demographic and socioeconomic factors. A total of 640 patients were included (aSAH group, 251; UIA group, 389). Significant associations were observed between race and ethnicity, SES, insurance type, and aneurysm rupture. Non-White race or ethnicity, lower SES, and having public or no insurance were associated with increased odds of aSAH presentation. The aSAH group had poorer functional outcomes and higher mortality rates than the UIA group. Patients who are non-White, have low SES, and have public or no insurance were disproportionately affected by aSAH, which is historically associated with poorer functional outcomes.
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- 2024
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6. Retraction Note: Pericyte loss influences Alzheimer-like neurodegeneration in mice
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Abhay P. Sagare, Robert D. Bell, Zhen Zhao, Qingyi Ma, Ethan A. Winkler, Anita Ramanathan, and Berislav V. Zlokovic
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Science - Published
- 2024
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7. Number Needing Review: A Novel Metric to Assess Triage Efficiency of Large Vessel Occlusion Detection Systems
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Joshua S. Catapano, Katriel E. Lee, Shashvat M. Desai, India C. Rangel, Henry O. Stonnington, Kavelin Rumalla, Caleb Rutledge, Visish M. Srinivasan, Jacob F. Baranoski, Tyler S. Cole, Ethan A. Winkler, Andrew F. Ducruet, Felipe C. Albuquerque, and Ashutosh P. Jadhav
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large vessel occlusion ,LVO ,mechanical thrombectomy ,RapidAI ,Neurology. Diseases of the nervous system ,RC346-429 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Endovascular thrombectomy is the gold‐standard treatment for large vessel occlusions (LVOs). A novel metric is introduced: the number needing review (NNR) to assess the triage efficiency of LVO detection systems. Methods Patients with suspected ischemic stroke and images processed by RapidAI LVO detection software over 6 months were reviewed. Only patients with LVOs of the M1 segment were included. The NNR was calculated for an M1 occlusion. Results Of 559 patients, M1 occlusion was detected in 42 patients (7.5%). RapidAI LVO had a sensitivity of 71%, specificity of 94%, positive predictive value of 49%, and negative predictive value of 92% for M1 occlusion. When gaze deviation and hyperdense sign were combined with RapidAI LVO, the specificity and positive predictive value increased to 100% for an M1 occlusion. A negative RapidAI LVO result combined with a low (6 seconds) or high (6 seconds) Tmax threshold was found to have a specificity and positive predictive value of 100% for no occlusion. The combination of gaze deviation, hyperdense sign, positive RapidAI LVO, and negative RapidAI LVO with low Tmax threshold yielded an NNR of 24 per 100 cases. When combined with a negative RapidAI LVO and a high Tmax threshold, the NNR was 16 per 100 cases. Adding National Institutes of Health Stroke Scale score 6 seconds threshold, the NNR is significantly reduced.
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- 2023
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8. A comprehensive assessment of self-reported symptoms among patients harboring an unruptured intracranial aneurysm
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Ashia M. Hackett, Stefan W. Koester, Emmajane G. Rhodenhiser, Lea Scherschinski, Jarrod D. Rulney, Anant Naik, Elsa Nico, Adam T. Eberle, Joelle N. Hartke, Brandon M. Fox, Ethan A. Winkler, Joshua S. Catapano, and Michael T. Lawton
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cerebrovascular ,microsurgical treatment ,retrospective analysis ,symptoms ,unruptured intracranial aneurysms ,Surgery ,RD1-811 - Abstract
BackgroundApproximately 3.2%–6% of the general population harbor an unruptured intracranial aneurysm (UIA). Ruptured aneurysms represent a significant healthcare burden, and preventing rupture relies on early detection and treatment. Most patients with UIAs are asymptomatic, and many of the symptoms associated with UIAs are nonspecific, which makes diagnosis challenging. This study explored symptoms associated with UIAs, the rate of resolution of such symptoms after microsurgical treatment, and the likely pathophysiology.MethodsA retrospective review of patients with UIAs who underwent microsurgical treatment from January 1, 2014, to December 31, 2020, at a single quaternary center were identified. Analyses included the prevalence of nonspecific symptoms upon clinical presentation and postoperative follow-up; comparisons of symptomatology by aneurysmal location; and comparisons of patient demographics, aneurysmal characteristics, and poor neurologic outcome at postoperative follow-up stratified by symptomatic versus asymptomatic presentation.ResultsThe analysis included 454 patients; 350 (77%) were symptomatic. The most common presenting symptom among all 454 patients was headache (n = 211 [46%]), followed by vertigo (n = 94 [21%]), cognitive disturbance (n = 68[15%]), and visual disturbance (n = 64 [14%]). Among 328 patients assessed for postoperative symptoms, 258 (79%) experienced symptom resolution or improvement.ConclusionThis cohort demonstrates that the clinical presentation of patients with UIAs can be associated with vague and nonspecific symptoms. Early detection is crucial to prevent aneurysmal subarachnoid hemorrhage. It is imperative that physicians not rule out aneurysms in the setting of nonspecific neurologic symptoms.
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- 2023
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9. Comparison of Neurological Outcome of Surgically Treated Brainstem Cavernous Malformations Following Single or Multiple Hemorrhages
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Olga Ciobanu-Caraus, Ethan A. Winkler, Anant Naik, Laura B. Lopez Lopez, Sahin Hanalioglu, Stefan W. Koester, Emmajane G. Rhodenhiser, Elsa Nico, Ashia Hackett, Joelle N. Hartke, Joshua S. Catapano, Robert F. Spetzler, and Michael T. Lawton
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Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2023
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10. Characteristics of Postoperative Outcome Clusters in Brainstem Cavernous Malformation Patients: An Unsupervised and Supervised Machine Learning Analysis
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Joshua S. Catapano, Anant Naik, Olga Ciobanu-Caraus, Laura B. Lopez Lopez, Ashia Hackett, E. Nico, Stefan W. Koester, Lea Scherschinski, Joelle N. Hartke, Brandon Fox, Ethan A. Winkler, Robert F. Spetzler, and Michael T. Lawton
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Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2023
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11. Hospital Cost for Transferred Patients With Large Vessel Occlusions Undergoing Endovascular Thrombectomy
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Joshua S. Catapano, Kavelin Rumalla, Brandon A. Nguyen, Ethan A. Winkler, Parth P. Parikh, Stefan W. Koester, Visish M. Srinivasan, Jacob F. Baranoski, Tyler S. Cole, Caleb Rutledge, Shashvat M. Desai, Andrew F. Ducruet, Felipe C. Albuquerque, and Ashutosh P. Jadhav
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direct to angiography suite ,hospital cost ,large vessel occlusion ,mechanical thrombectomy ,Neurology. Diseases of the nervous system ,RC346-429 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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12. Safety and Efficacy of Radial Versus Femoral Artery Access for Mechanical Thrombectomy Procedures Following Intravenous Administration of Tissue Plasminogen Activator
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Joshua S. Catapano, Kavelin Rumalla, Dara S. Farhadi, Parth P. Parikh, Brandon A. Nguyen, Caleb Rutledge, Visish M. Srinivasan, Jacob F. Baranoski, Tyler S. Cole, Ethan A. Winkler, Shashvat M. Desai, Andrew F. Ducruet, Felipe C. Albuquerque, and Ashutosh P. Jadhav
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femoral artery access ,mechanical thrombectomy ,radial artery access ,tissue plasminogen activator ,Neurology. Diseases of the nervous system ,RC346-429 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background The transradial artery (TRA) approach for neuroendovascular procedures is a safe and effective alternative to the transfemoral artery (TFA) approach. We compared the efficiency and periprocedural outcomes of TRA and TFA approaches for acute stroke interventions in patients receiving intravenous tissue plasminogen activator. Methods A retrospective cohort study analyzed data from patients at a large cerebrovascular center from January 1, 2014, to March 31, 2021. Baseline characteristics, periprocedural efficiency and efficacy, and in‐hospital outcomes were compared between intervention cohorts (TRA and TFA). Results Of 314 patients analyzed, 21 (7%) underwent a TRA approach and 293 (93%) underwent a TFA approach. Complications occurred in one (5%) of 21 patients in the TRA cohort and 20 (7%) of 293 patients in the TFA cohort. Access site complications were present in 12 (4%) patients with TFA, and no patients with TRA experienced access site complications. The mean length of stay was significantly longer for the TFA cohort (8.8 days [standard deviation, 8.5 days]) versus the TRA cohort (4.8 days [standard deviation, 2.9 days]) (P=0.02). Linear regression analysis showed that femoral access, Medicaid insurance, and discharge National Institutes of Health Stroke Scale score >10 predicted longer length of stay (P≤0.046). However, when the time to initial physical or occupational therapy session was added to the model, access site was no longer significant (P=0.42). Conclusion The TRA approach may reduce periprocedural complications and hospital length of stay compared with the TFA approach. The shorter length of stay associated with TRA access appeared to be associated with earlier initiation of physical or occupational therapies.
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- 2022
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13. Endovascular Biopsy for Detection of Somatic Mosaicism in Human Fusiform Cerebral Aneurysms
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Joseph H. Garcia, Ethan A. Winkler, Kerstin Müller, Evan Kao, Kazim Narsinh, Nerissa Ko, Patricia Cornett, Adib A. Abla, Joseph T. Shieh, and Daniel L. Cooke
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Neurology. Diseases of the nervous system ,RC346-429 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2022
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14. Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa
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Kazim H. Narsinh, Kamileh Narsinh, David B. McCoy, Zhengda Sun, Cathra Halabi, Karl Meisel, Tarik Tihan, Krishna Chaganti, Matthew R. Amans, Van V. Halbach, Randall T. Higashida, Steven W. Hetts, Christopher F. Dowd, Ethan A. Winkler, Adib A. Abla, Tomasz J. Nowakowski, and Daniel L. Cooke
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fusiform aneurysm ,gene expression profile ,single cell RNA sequencing (scRNA-seq) ,polyarteritis nodosa (PAN) ,endovascular biopsy ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.
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- 2021
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15. The Expanding Cell Diversity of the Brain Vasculature
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Jayden M. Ross, Chang Kim, Denise Allen, Elizabeth E. Crouch, Kazim Narsinh, Daniel L. Cooke, Adib A. Abla, Tomasz J. Nowakowski, and Ethan A. Winkler
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neurovascular unit ,single cell sequencing ,endothelial cells ,pericytes and vascular smooth muscle cells ,perivascular macrophages ,perivascular fibroblasts ,Physiology ,QP1-981 - Abstract
The cerebrovasculature is essential to brain health and is tasked with ensuring adequate delivery of oxygen and metabolic precursors to ensure normal neurologic function. This is coordinated through a dynamic, multi-directional cellular interplay between vascular, neuronal, and glial cells. Molecular exchanges across the blood–brain barrier or the close matching of regional blood flow with brain activation are not uniformly assigned to arteries, capillaries, and veins. Evidence has supported functional segmentation of the brain vasculature. This is achieved in part through morphologic or transcriptional heterogeneity of brain vascular cells—including endothelium, pericytes, and vascular smooth muscle. Advances with single cell genomic technologies have shown increasing cell complexity of the brain vasculature identifying previously unknown cell types and further subclassifying transcriptional diversity in cardinal vascular cell types. Cell-type specific molecular transitions or zonations have been identified. In this review, we summarize emerging evidence for the expanding vascular cell diversity in the brain and how this may provide a cellular basis for functional segmentation along the arterial-venous axis.
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- 2020
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16. Circadian variability of the initial Glasgow Coma Scale score in traumatic brain injury patients
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John K. Yue, Caitlin K. Robinson, Ethan A. Winkler, Pavan S. Upadhyayula, John F. Burke, Romain Pirracchio, Catherine G. Suen, Hansen Deng, Laura B. Ngwenya, Sanjay S. Dhall, Geoffrey T. Manley, and Phiroz E. Tarapore
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Biology (General) ,QH301-705.5 - Abstract
Introduction: The Glasgow Coma Scale (GCS) score is the primary method of assessing consciousness after traumatic brain injury (TBI), and the clinical standard for classifying TBI severity. There is scant literature discerning the influence of circadian rhythms or emergency department (ED) arrival hour on this important clinical tool. Methods: Retrospective cohort analysis of adult patients suffering blunt TBI using the National Sample Program of the National Trauma Data Bank, years 2003–2006. ED arrival GCS score was characterized by midday (10 a.m.–4 p.m.) and midnight (12 a.m.–6 a.m.) cohorts (N=24548). Proportions and standard errors are reported for descriptive data. Multivariable regressions using odds ratios (OR), mean differences (B), and their associated 95% confidence intervals [CI] were performed to assess associations between ED arrival hour and GCS score. Statistical significance was assessed at p
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- 2017
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17. Pre-injury Comorbidities Are Associated With Functional Impairment and Post-concussive Symptoms at 3- and 6-Months After Mild Traumatic Brain Injury: A TRACK-TBI Study
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John K. Yue, Maryse C. Cnossen, Ethan A. Winkler, Hansen Deng, Ryan R. L. Phelps, Nathan A. Coss, Sourabh Sharma, Caitlin K. Robinson, Catherine G. Suen, Mary J. Vassar, David M. Schnyer, Ava M. Puccio, Raquel C. Gardner, Esther L. Yuh, Pratik Mukherjee, Alex B. Valadka, David O. Okonkwo, Hester F. Lingsma, Geoffrey T. Manley, TRACK-TBI Investigators, Shelly R. Cooper, Kristen Dams-O’Connor, Wayne A. Gordon, Allison J. Hricik, Andrew I. R. Maas, David K. Menon, and Diane J. Morabito
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functional impairment ,mild traumatic brain injury ,post-concussive symptoms ,pre-injury comorbidities ,prognosis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Introduction: Over 70% of traumatic brain injuries (TBI) are classified as mild (mTBI), which present heterogeneously. Associations between pre-injury comorbidities and outcomes are not well-understood, and understanding their status as risk factors may improve mTBI management and prognostication.Methods: mTBI subjects (GCS 13–15) from TRACK-TBI Pilot completing 3- and 6-month functional [Glasgow Outcome Scale-Extended (GOSE)] and post-concussive outcomes [Acute Concussion Evaluation (ACE) physical/cognitive/sleep/emotional subdomains] were extracted. Pre-injury comorbidities >10% incidence were included in regressions for functional disability (GOSE ≤ 6) and post-concussive symptoms by subdomain. Odds ratios (OR) and mean differences (B) were reported. Significance was assessed at p < 0.0083 (Bonferroni correction).Results: In 260 subjects sustaining blunt mTBI, mean age was 44.0-years and 70.4% were male. Baseline comorbidities >10% incidence included psychiatric-30.0%, cardiac (hypertension)-23.8%, cardiac (structural/valvular/ischemic)-20.4%, gastrointestinal-15.8%, pulmonary-15.0%, and headache/migraine-11.5%. At 3- and 6-months separately, 30.8% had GOSE ≤ 6. At 3-months, psychiatric (GOSE ≤ 6: OR = 2.75, 95% CI [1.44–5.27]; ACE-physical: B = 1.06 [0.38–1.73]; ACE-cognitive: B = 0.72 [0.26–1.17]; ACE-sleep: B = 0.46 [0.17–0.75]; ACE-emotional: B = 0.64 [0.25–1.03]), headache/migraine (GOSE ≤ 6: OR = 4.10 [1.67–10.07]; ACE-sleep: B = 0.57 [0.15–1.00]; ACE-emotional: B = 0.92 [0.35–1.49]), and gastrointestinal history (ACE-physical: B = 1.25 [0.41–2.10]) were multivariable predictors of worse outcomes. At 6-months, psychiatric (GOSE ≤ 6: OR = 2.57 [1.38–4.77]; ACE-physical: B = 1.38 [0.68–2.09]; ACE-cognitive: B = 0.74 [0.28–1.20]; ACE-sleep: B = 0.51 [0.20–0.83]; ACE-emotional: B = 0.93 [0.53–1.33]), and headache/migraine history (ACE-physical: B = 1.81 [0.79–2.84]) predicted worse outcomes.Conclusions: Pre-injury psychiatric and pre-injury headache/migraine symptoms are risk factors for worse functional and post-concussive outcomes at 3- and 6-months post-mTBI. mTBI patients presenting to acute care should be evaluated for psychiatric and headache/migraine history, with lower thresholds for providing TBI education/resources, surveillance, and follow-up/referrals.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01565551.
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- 2019
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18. Calvarial aneurysmal bone cyst associated with fibrous dysplasia: Case report and literature review
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Harjus Birk, B.S., Ethan A. Winkler, M.D. Ph.D., Phillip A. Bonney, B.S., Mitchel S. Berger, M.D., and Michael W. McDermott, M.D.
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Bone cyst ,Calvarium ,McCune-Albright syndrome ,In situ cranioplasty ,Cosmesis ,Surgery ,RD1-811 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Aneurysmal bone cysts are benign, expansile bone lesions primary or secondary to other pathology. The majority are seen in long bones and the spine, rarely occurring within the cranial vault. Here we describe the case of a 17-year-old gentleman with McCune-Albright syndrome who developed a right parietal aneurysmal bone cyst in the setting of fibrous dysplasia. The patient was treated with lesion excision and in situ cranioplasty using methyl methacrylate and molded titanium mesh, ultimately rendering excellent cosmetic outcome. Our case report highlights the efficacy of in situ titanium cranioplasties in contouring to the native skull and enabling optimization of cosmesis, specifically through the use of titanium mesh plates with the bone flap as a template.
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- 2017
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19. RETRACTED ARTICLE: Pericyte loss influences Alzheimer-like neurodegeneration in mice
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Abhay P. Sagare, Robert D. Bell, Zhen Zhao, Qingyi Ma, Ethan A. Winkler, Anita Ramanathan, and Berislav V. Zlokovic
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Science - Abstract
Abstract Pericytes are cells in the blood–brain barrier that degenerate in Alzheimer’s disease (AD), a neurological disorder associated with neurovascular dysfunction, abnormal elevation of amyloid β-peptide (Aβ), tau pathology and neuronal loss. Whether pericyte degeneration can influence AD-like neurodegeneration and contribute to disease pathogenesis remains, however, unknown. Here we show that in mice overexpressing Aβ-precursor protein, pericyte loss elevates brain Aβ40 and Aβ42 levels and accelerates amyloid angiopathy and cerebral β-amyloidosis by diminishing clearance of soluble Aβ40 and Aβ42 from brain interstitial fluid prior to Aβ deposition. We further show that pericyte deficiency leads to the development of tau pathology and an early neuronal loss that is normally absent in Aβ-precursor protein transgenic mice, resulting in cognitive decline. Our data suggest that pericytes control multiple steps of AD-like neurodegeneration pathogenic cascade in Aβ-precursor protein-overexpressing mice. Therefore, pericytes may represent a novel therapeutic target to modify disease progression in AD.
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- 2013
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20. Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence
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John K. Yue, John F. Burke, Pavan S. Upadhyayula, Ethan A. Winkler, Hansen Deng, Caitlin K. Robinson, Romain Pirracchio, Catherine G. Suen, Sourabh Sharma, Adam R. Ferguson, Laura B. Ngwenya, Murray B. Stein, Geoffrey T. Manley, and Phiroz E. Tarapore
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cognition ,depression ,meta-analysis ,postconcussive disorder ,selective serotonin reuptake inhibitor ,sleep disturbance ,traumatic brain injury ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%–50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo—a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.
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- 2017
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21. You Take the Low Road: Differential Outcomes After Tangential and Transcortical Approaches to Medial Temporal Brain Arteriovenous Malformations
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Lea Scherschinski, Visish M. Srinivasan, Katherine Karahalios, Joseph H. Garcia, Stefan W. Koester, Jubran H. Jubran, Dimitri Benner, Ethan A. Winkler, Joshua S. Catapano, Mohamed A. Labib, Christopher S. Graffeo, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Published
- 2023
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22. A taxonomy for deep cerebral cavernous malformations: subtypes of thalamic lesions
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Joshua S. Catapano, Kavelin Rumalla, Visish M. Srinivasan, Dimitri Benner, Ethan A. Winkler, Peter M. Lawrence, Kristen Larson Keil, and Michael T. Lawton
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General Medicine - Abstract
OBJECTIVE Anatomical taxonomy is a practical tool to successfully guide clinical decision-making for patients with brain arteriovenous malformations and brainstem cavernous malformations (CMs). Deep cerebral CMs are complex, difficult to access, and highly variable in size, shape, and position. The authors propose a novel taxonomic system for deep CMs in the thalamus based on clinical presentation (syndromes) and anatomical location (identified on MRI). METHODS The taxonomic system was developed and applied to an extensive 2-surgeon experience from 2001 through 2019. Deep CMs involving the thalamus were identified. These CMs were subtyped on the basis of the predominant surface presentation identified on preoperative MRI. Six subtypes among 75 thalamic CMs were defined: anterior (7/75, 9%), medial (22/75, 29%), lateral (10/75, 13%), choroidal (9/75, 12%), pulvinar (19/75, 25%), and geniculate (8/75, 11%). Neurological outcomes were assessed using modified Rankin Scale (mRS) scores. A postoperative score ≤ 2 was defined as a favorable outcome and > 2 as a poor outcome. Clinical and surgical characteristics and neurological outcomes were compared among subtypes. RESULTS Seventy-five patients underwent resection of thalamic CMs and had clinical and radiological data available. Their mean age was 40.9 (SD 15.2) years. Each thalamic CM subtype was associated with a recognizable constellation of neurological symptoms. The common symptoms were severe or worsening headaches (30/75, 40%), hemiparesis (27/75, 36%), hemianesthesia (21/75, 28%), blurred vision (14/75, 19%), and hydrocephalus (9/75, 12%). The thalamic CM subtype determined the selection of surgical approach. A single approach was associated with each subtype for most patients. The main exception to this paradigm was that in the surgeons’ early experience, pulvinar CMs were resected through a superior parietal lobule–transatrial approach (4/19, 21%), which later evolved to the paramedian supracerebellar-infratentorial approach (12/19, 63%). Relative outcomes implied by mRS scores were unchanged or improved in most patients (61/66, 92%) postoperatively. CONCLUSIONS This study confirms the authors’ hypothesis that this taxonomy for thalamic CMs can meaningfully guide the selection of surgical approach and resection strategy. The proposed taxonomy can increase diagnostic acumen at the patient bedside, help identify optimal surgical approaches, enhance the clarity of clinical communications and publications, and improve patient outcomes.
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- 2023
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23. Socioeconomic Drivers of Outcomes After Aneurysmal Subarachnoid Hemorrhage Treatment at a Large Comprehensive Stroke Center
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Kavelin Rumalla, Joshua S. Catapano, Varun Mahadevan, Samuel R. Sorkhi, Stefan W. Koester, Ethan A. Winkler, Christopher S. Graffeo, Visish M. Srinivasan, Ruchira M. Jha, Ashutosh P. Jadhav, Andrew F. Ducruet, Felipe C. Albuquerque, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Published
- 2023
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24. Approach Selection Strategies for Repeat Resection of Brain Cavernous Malformations: Cohort Study
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Christopher S. Graffeo, Lea Scherschinski, Dimitri Benner, Diego A. Devia, George Thomas, Stefan W. Koester, Joshua S. Catapano, Ethan A. Winkler, Visish M. Srinivasan, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Published
- 2023
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25. A comparison of incidental and symptomatic unruptured brain arteriovenous malformations in children
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Alex Y. Lu, Ethan A. Winkler, Joseph H. Garcia, Kunal P. Raygor, Heather J. Fullerton, Christine K. Fox, Helen Kim, Kurtis I. Auguste, Peter P. Sun, Steven W. Hetts, Michael T. Lawton, Adib A. Abla, and Nalin Gupta
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General Medicine - Abstract
OBJECTIVE Patients with unruptured brain arteriovenous malformations (AVMs) may present with headaches, seizures, and/or neurological deficits. A smaller number of cases may be discovered incidentally. These lesions remain incompletely understood due to their sparse reporting. Herein, the authors describe the largest series to date comparing the presentation, angioarchitecture, and management of incidental versus symptomatic unruptured AVMs in children. METHODS The authors performed a retrospective analysis of patients who presented with brain AVMs from 1998 to 2022 at the University of California, San Francisco. Inclusion criteria were age ≤ 18 years at the time of presentation and an angiographically proven unruptured AVM that had been diagnosed postnatally. RESULTS Of 76 children with unruptured AVMs, 66 (86.8%) presented with headaches, seizures, and/or neurological deficit. Ten AVMs (13.1%) were incidentally discovered through unrelated disease workup (50%), cranial trauma (40%), or research study participation (10%). Compared with patients with symptomatic unruptured AVMs, patients with incidental unruptured AVMs had a smaller mean ± SD maximum nidus diameter (2.82 ± 1.1 vs 3.98 ± 1.52 cm, p = 0.025) and fewer had deep venous drainage (20% of patients vs 61%, p = 0.036). They also presented at an earlier age (10 ± 5.2 vs 13.5 ± 4 years, p = 0.043) and with longer duration to first treatment (541 ± 922 vs 196 ± 448 days, p = 0.005). During the observation period, 1 patient developed recurring headaches and demonstrated AVM nidus growth. Four AVMs greater than 3 cm in size or in a deep location were treated with radiosurgery. Six other AVMs were treated with resection, with 2 receiving preoperative embolization. Eight AVMs (80%) were obliterated on last follow-up. Postprocedural complications included 2 transient neurological deficits after resection and 1 case of delayed seizure development after radiosurgery. The mean follow-up period was 5.7 ± 5.7 years without any hemorrhage episodes. CONCLUSIONS A substantial proportion of pediatric patients with unruptured AVMs are discovered incidentally. With earlier presentation and more elementary angioarchitecture than symptomatic unruptured AVMs, these incidental lesions provide a snapshot into the natural history of AVM before symptom development or rupture.
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- 2023
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26. Propensity-adjusted analysis of ultra-early aneurysmal subarachnoid hemorrhage treatment and patient outcomes
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Stefan W. Koester, Joshua S. Catapano, Emmajane G. Rhodenhiser, Robert F. Rudy, Ethan A. Winkler, Dimitri Benner, Tyler S. Cole, Jacob F. Baranoski, Visish M. Srinivasan, Christopher S. Graffeo, Ruchira M. Jha, Ashutosh P. Jadhav, Andrew F. Ducruet, Felipe C. Albuquerque, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Published
- 2023
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27. Analysis of the Weekend Effect at a High-Volume Center for the Treatment of Intracranial Aneurysms
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Stefan W. Koester, Joshua S. Catapano, Kavelin Rumalla, Visish M. Srinivasan, Emmajane G. Rhodenhiser, Joelle N. Hartke, Dimitri Benner, Ethan A. Winkler, Tyler S. Cole, Jacob F. Baranoski, Ashutosh P. Jadhav, Andrew F. Ducruet, Felipe C. Albuquerque, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Abstract
The "weekend effect" is the negative effect on disease course and treatment resulting from being admitted to the hospital during a weekend. Whether the weekend effect is associated with worse outcomes for patients treated for aneurysmal subarachnoid hemorrhage (aSAH) is unknown. We assessed neurologic outcomes of patients with aSAH admitted during the weekend versus during the week.A retrospective database was reviewed to identify all patients with aSAH who received open or endovascular treatment from August 1, 2007, to July 31, 2019, at a quaternary center. The primary outcome was a poor neurologic outcome (modified Rankin Scale score2). Propensity adjustment included age, sex, treatment type, Hunt and Hess grade, and Charlson Comorbidity Index.A total of 1014 patients (women, 703 [69.3%]; men, 311 [30.7%]; mean age, 56 [standard deviation, 14]) met inclusion criteria; 726 (71.6%) had weekday admissions, and 288 (28.4%) had weekend admissions. There was no significant difference between patients with a weekday versus a weekend admission in mean (standard deviation) time to treatment (0.85 [1.29] vs. 0.93 [1.30] days, P = 0.10) or length of stay (19 [9] vs. 19 [9] days, P = 0.04). Total cost and rates of delayed cerebral ischemia and vasospasm were similar between the admission groups, both overall and within the open and endovascular treatment cohorts. After propensity adjustment, weekend admission was not a significant predictor of a modified Rankin Scale score greater than 2 (odds ratio [95% confidence interval]; 1.12 [0.85-1.49]; P = 0.4).No difference in neurologic outcomes was associated with weekend admission among this cohort of patients with aSAH.
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- 2023
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28. Health Care Expenditures Associated with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage: A Propensity-Adjusted Analysis
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Stefan W. Koester, Joshua S. Catapano, Kavelin Rumalla, Stephen J. Dabrowski, Dimitri Benner, Ethan A. Winkler, Tyler S. Cole, Jacob F. Baranoski, Visish M. Srinivasan, Christopher S. Graffeo, Ruchira M. Jha, Ashutosh P. Jadhav, Andrew F. Ducruet, Felipe C. Albuquerque, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Abstract
The additional hospital costs associated with delayed cerebral ischemia (DCI) have not been well investigated in prior literature. In this study, the total hospital cost of DCI in aneurysmal subarachnoid hemmorhage (aSAH) patients treated at a single quaternary center was analyzed.All patients in the Post-Barrow Ruptured Aneurysm Trial treated for an aSAH between January 1, 2014, and July 31, 2019, were retrospectively analyzed. DCI was defined as cerebral infarction identified on computed tomography, magnetic resonance imaging, or autopsy after exclusion of procedure-related infarctions. The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis. Propensity score covariate-adjusted linear regression analysis included age, sex, open versus endovascular treatment, Hunt and Hess score, and Charlson Comorbidity Index score.Of the 391 patients included, 144 (37%) had DCI. Patients with DCI had a significantly greater cost compared to patients without DCI (mean standard deviation $112,081 [$54,022] vs. $86,159 [$38,817]; P 0.001) and a significantly greater length of stay (21 days [11] vs. 18 days [8], P = 0.003, respectively). In propensity-adjusted linear regression analysis, both DCI (odds ratio, $13,871; 95% confidence interval, $7558-$20,185; P 0.001) and length of stay (odds ratio, $3815 per day; 95% confidence interval, $3480-$4149 per day; P 0.001) were found to significantly increase the cost.The significantly higher costs associated with DCI further support the evidence that adverse effects associated with DCI in aSAH pose a significant burden to the health care system.
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- 2022
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29. Liver Cirrhosis and Inpatient Mortality in Aneurysmal Subarachnoid Hemorrhage: A Propensity-Adjusted Analysis
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Joshua S. Catapano, Katriel E. Lee, Kavelin Rumalla, Visish M. Srinivasan, Tyler S. Cole, Jacob F. Baranoski, Ethan A. Winkler, Christopher S. Graffeo, Muhaiman Alabdly, Ruchira M. Jha, Ashutosh P. Jadhav, Andrew F. Ducruet, Felipe C. Albuquerque, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Abstract
Liver cirrhosis is associated with an increased risk of aneurysmal subarachnoid hemorrhage (aSAH). However, large studies analyzing the prognosis of cirrhotic patients after aSAH treatment are lacking. This study explores factors associated with inpatient mortality among aSAH patients with cirrhosis.All patients who underwent open or endovascular treatment for an aSAH at a large quaternary center between January 1, 2003, and July 31, 2019, were retrospectively reviewed. Patients were grouped into cirrhosis versus noncirrhosis groups. Univariate analysis determined variables associated with inpatient mortality. Variables with P0.20 were included in a propensity-adjusted multivariable logistic regression analysis to predict inpatient mortality.A total of 1419 patients were treated for aSAH; 17 (1.2%) had confirmed cirrhosis. Inpatient mortality was significantly higher among cirrhotic patients than noncirrhotic patients (35.3% vs. 6.8%; P0.001). In the univariate analysis for inpatient mortality, the variables cirrhosis, age65 years, Charlson Comorbidity Index4, aneurysm size ≥10 mm, Hunt and Hess grade3, Fisher grade 4, delayed cerebral ischemia (DCI), and posterior circulation aneurysm had P0.20 and were included in the multivariable analysis. The propensity-adjusted stepwise multivariable logistic regression analysis showed that cirrhosis (odds ratio [OR]: 12.7, 95% confidence interval [CI]: 3.3-48.7), Hunt and Hess grade3 (OR: 3.9, 95% CI: 2.3-6.4), Fisher grade 4 (OR: 3.7, 95% CI: 1.3-10.7), and DCI (OR: 2.4, 95% CI: 1.5-3.9) were associated with inpatient mortality (P ≤ 0.01).Cirrhosis was a predictor of inpatient mortality among aSAH patients and was a stronger predictor than DCI or a poor Hunt and Hess grade among patients in this study.
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- 2022
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30. Safety of brainstem safe entry zones: comparison of microsurgical outcomes associated with superficial, exophytic, and deep brainstem cavernous malformations
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Joshua S. Catapano, Dimitri Benner, Emmajane G. Rhodenhiser, Kavelin Rumalla, Christopher S. Graffeo, Visish M. Srinivasan, Ethan A. Winkler, and Michael T. Lawton
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General Medicine - Abstract
OBJECTIVE Safe entry zones (SEZs) enable safe tissue transgression to lesions beneath the brainstem surface. However, evidence for the safety of SEZs is scarce and is based on anatomical studies, case reports, and small series. METHODS A cohort of 154 patients who underwent microsurgical brainstem cavernous malformation (BSCM) treatment during a 23-year period and who had preoperative MR images and intraoperative photographs or videos was retrospectively examined. This study assessed the safety of SEZs for access to deep BSCMs, preoperative MRI to predict BSCM surface proximity, and the relationships between BSCM subtype, surgical approach, and SEZs. Lesions were characterized as exophytic, superficial, or deep on the basis of preoperative MRI and intraoperative inspection. Outcomes were scored as good (modified Rankin Scale [mRS] score ≤ 2) or poor (mRS score > 2) and relative outcomes as stable/improved or worse relative to baseline (± 1 point). RESULTS Resections included 34 (22%) in the midbrain, 102 (66%) in the pons, and 18 (12%) in the medulla. Of those, 23 (15%) were exophytic, 57 (37%) were superficial, and 74 (48%) were deep. Established SEZs were used for 97% (n = 72) of deep lesions; the preferred SEZ associated with its subtype was used for 91% (n = 67). MR images accurately depicted exophytic BSCMs that did not require SEZ approaches (sensitivity, 96%) but overestimated the proximity of lesions superficial to brainstem surfaces (specificity, 67%), resulting in unanticipated SEZ use. Final neurological outcomes were good in 80% of patients with follow-up data (119/149), and relative outcomes were stable/improved in 93% (139/149). Outcomes for patients with brainstem transgression through an SEZ did not differ from outcomes for patients with superficial or exophytic lesions that did not require SEZ use (final mRS score ≤ 2 in 72% of all patients with deep lesions vs 82% of all patients with superficial or exophytic lesions [p = 0.10]). Among patients with follow-up, the rates of permanent new cranial nerve deficits in patients with deep BSCMs and superficial or exophytic BSCMs were 21% and 20%, respectively (p = 0.81), with no significant change in overall cranial nerve deficit (0 and −1, p = 0.65). CONCLUSIONS Neurological outcomes for patients with deep BSCMs were equivalent to those for superficial or exophytic BSCMs, validating the safety of SEZs for deep BSCMs. Preoperative T1-weighted MR images overestimated the lesion’s surface proximity, necessitating detailed knowledge of SEZs and readiness to use them in cases of radiological-microsurgical discordance. Most patients achieved favorable outcomes despite the transgression of eloquent brainstem tissue in and around SEZs.
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- 2022
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31. Localized conditional induction of brain arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia
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Lea Scherschinski, Chul Han, Yong Hwan Kim, Ethan A. Winkler, Joshua S. Catapano, Tyler D. Schriber, Peter Vajkoczy, Michael T. Lawton, and S. Paul Oh
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Cancer Research ,Physiology ,Clinical Biochemistry - Abstract
Background Longitudinal mouse models of brain arteriovenous malformations (AVMs) are crucial for developing novel therapeutics and pathobiological mechanism discovery underlying brain AVM progression and rupture. The sustainability of existing mouse models is limited by ubiquitous Cre activation, which is associated with lethal hemorrhages resulting from AVM formation in visceral organs. To overcome this condition, we developed a novel experimental mouse model of hereditary hemorrhagic telangiectasia (HHT) with CreER-mediated specific, localized induction of brain AVMs. Methods Hydroxytamoxifen (4-OHT) was stereotactically delivered into the striatum, parietal cortex, or cerebellum of R26CreER; Alk12f/2f (Alk1-iKO) littermates. Mice were evaluated for vascular malformations with latex dye perfusion and 3D time-of-flight magnetic resonance angiography (MRA). Immunofluorescence and Prussian blue staining were performed for vascular lesion characterization. Results Our model produced two types of brain vascular malformations, including nidal AVMs (88%, 38/43) and arteriovenous fistulas (12%, 5/43), with an overall frequency of 73% (43/59). By performing stereotaxic injection of 4-OHT targeting different brain regions, Alk1-iKO mice developed vascular malformations in the striatum (73%, 22/30), in the parietal cortex (76%, 13/17), and in the cerebellum (67%, 8/12). Identical application of the stereotaxic injection protocol in reporter mice confirmed localized Cre activity near the injection site. The 4-week mortality was 3% (2/61). Seven mice were studied longitudinally for a mean (SD; range) duration of 7.2 (3; 2.3−9.5) months and demonstrated nidal stability on sequential MRA. The brain AVMs displayed microhemorrhages and diffuse immune cell invasion. Conclusions We present the first HHT mouse model of brain AVMs that produces localized AVMs in the brain. The mouse lesions closely resemble the human lesions for complex nidal angioarchitecture, arteriovenous shunts, microhemorrhages, and inflammation. The model’s longitudinal robustness is a powerful discovery resource to advance our pathomechanistic understanding of brain AVMs and identify novel therapeutic targets.
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- 2023
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32. Cost-Effectiveness of Forgoing Postoperative Catheter Angiography After Microsurgical Occlusion of Spinal Dorsal Intradural Arteriovenous Fistulas
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Lea Scherschinski, Katherine Karahalios, Visish M. Srinivasan, Joshua S. Catapano, Jubran H. Jubran, Dimitri Benner, Kavelin Rumalla, Ethan A. Winkler, Christopher S. Graffeo, and Michael T. Lawton
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Surgery ,Neurology (clinical) - Published
- 2023
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33. Outcomes in patients with aneurysmal subarachnoid hemorrhage receiving sulfonylureas: a propensity-adjusted analysis
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Joshua S. Catapano, Stefan W. Koester, Kamila M. Bond, Visish M. Srinivasan, Dara S. Farhadi, Kavelin Rumalla, Tyler S. Cole, Jacob F. Baranoski, Ethan A. Winkler, Christopher S. Graffeo, Amanda Muñoz-Casabella, Ashutosh P. Jadhav, Andrew F. Ducruet, Felipe C. Albuquerque, Michael T. Lawton, and Ruchira M. Jha
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Surgery ,Neurology (clinical) - Published
- 2023
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34. Validation of the Ruptured Arteriovenous Malformation Grading Scale in a pediatric cohort
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Joseph H. Garcia, Caleb Rutledge, Ethan A. Winkler, Luis Carrete, Ramin A. Morshed, Alex Y. Lu, Satvir Saggi, Christine K. Fox, Heather J. Fullerton, Helen Kim, Daniel L. Cooke, Steven W. Hetts, Michael T. Lawton, Nalin Gupta, and Adib A. Abla
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Intracranial Arteriovenous Malformations ,Pediatric ,Neurology & Neurosurgery ,arteriovenous malformation ,vascular disease ,General Medicine ,vascular disorders ,Aneurysm ,Ruptured ,Brain Disorders ,Stroke ,Paediatrics and Reproductive Medicine ,Treatment Outcome ,ROC Curve ,disability ,Clinical Research ,Humans ,Child ,Intracranial Hemorrhages ,Retrospective Studies - Abstract
OBJECTIVE Pediatric brain arteriovenous malformations (AVMs) are the leading cause of spontaneous intracranial hemorrhage (SICH) in children. Although the incidence of SICH is low in pediatric populations, such events cause substantial morbidity. The recently created Ruptured Arteriovenous Malformation Grading Scale (RAGS) is proposed as a reliable and novel grading system to specifically serve as a predictor of clinical outcomes in patients following AVM rupture, similar to the Hunt and Hess (HH) grade for ruptured aneurysms. While these data are promising, pediatric patients were notably absent from the original study validating the RAGS. Therefore, correlation of the RAGS score with clinical outcomes following AVM rupture in individuals younger than 18 years of age using the RAGS score is needed. The objective of this study was to validate the RAGS in a cohort of pediatric patients with AVMs who presented with hemorrhage, thereby demonstrating the score’s generalizability, and expanding its external validity. METHODS A cohort of children with ruptured AVMs were retrospectively reviewed. Using disability, measured by the modified Rankin Scale (mRS), as the response variable, the area under the receiver operating characteristic curve (AUROC) was calculated for patients based on their RAGS scores for three time periods. The AUROC values were then compared with those generated by two commonly used clinical grading systems, the HH classification and Glasgow Coma Scale. RESULTS A total of 81 children who presented with ruptured AVMs were included in the study, with a mean follow-up duration of 4 years. The RAGS score outperformed other clinical grading scales in predicting mRS scores, with AUROC values of 0.81, 0.82, and 0.81 at three distinct follow-up periods. CONCLUSIONS The RAGS score correlated well with the clinical outcome after AVM rupture in pediatric patients. Additional validation studies across multiple treatment centers are needed to further demonstrate the generalizability of the scoring system.
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- 2022
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35. Sex-dependent manifestations of intracranial aneurysms
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Thomas Wälchli, Martin Ndengera, Paul E. Constanthin, Jeroen Bisschop, Sandrine Morel, Oliver Gautschi, Moncef Berhouma, Aristotelis Kalyvas, Philippe P. Monnier, Ethan A. Winkler, Hans Kortman, Kartik Bhatia, Philipp Dammann, Max Jägersberg, Renato Gondar, Karl Schaller, Brenda R. Kwak, and Philippe Bijlenga
- Abstract
BackgroundIntracranial aneurysms (IAs) are more common in females than in males, however, there is still very limited knowledge on sex-dependent differences regarding aneurysm location, multiplicity, rupture risk, risk factors and histopathology.MethodsThis prospective, consecutive cohort study examined whether IAs differ in multiplicity, location, geometry, rupture risk, risk factors and histology between sexes.ResultsWe included 982 patients (714 women, 268 men) totaling 1484 IAs (1056 unruptured, 397 ruptured). Three hundred sixty-three patients (36.97%) had multiple IAs, the proportion of which was significantly higher in females. In women, the ICA (40.79%) was the most frequent location for IAs, whereas in men most were found along the ACA territory (32.86%). Men were significantly more often diagnosed with ruptured aneurysms. Aneurysm geometry did not differ between sexes, however, ruptured aneurysms in men presented with a significantly larger neck diameter than unruptured ones. Regarding risk factors for aneurysm rupture, blood pressure control was more effective in women, whereas the effect of smoking status did not show clear sex-dependent differences. Histologically, wall-type classification analysis showed significantly more severe aneurysm wall types in men.ConclusionIA prevalence in women is significantly higher than in men. Women more often present with multiple IAs whereas men were more often diagnosed with ruptured IAs. Sex-specific differences in IA location were identified whereas geometry of IAs did not differ between sexes. IAs in men showed a more severe histological wall type. Further research is needed to unravel the molecular mechanisms underlying these important sex-dependent manifestations in IAs.
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- 2023
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36. Abstract 52: Prevalence Of Somatic Activating Kras Mutations In Pediatric And Adult Sporadic Brain Arteriovenous Malformations
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Ethan A Winkler, Joseph Garcia, Cynthia Tsang, Jeffrey Nelson, Charles McCulloch, Shantel Weinsheimer, Christine K Fox, Heather Fullerton, Nerissa Ko, Hua Su, Tomasz Nowakowski, Daniel L Cooke, Steven Hetts, Ekin Guney, MELIKE PEKMEZCI, Tarik Tihan, Michael Lawton, Adib Abla, Nalin Gupta, and Helen Kim
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Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Sporadic brain arteriovenous malformations (bAVMs) are a potentially treatable cause of stroke disproportionately affecting young people. Non-inherited somatic activating mutations in KRAS have been reported in ~50% of bAVM specimens primarily from adults. We hypothesized that KRAS mutations would be associated with an earlier age at diagnosis, larger bAVM size, or earlier time to hemorrhage. Methods: Sporadic bAVM tissue and clinical data were collected from patients seen at our institution. Genotyping was performed by digital droplet polymerase chain reaction to detect KRAS mutations (p.G12D, p.G12V or p.Q61H) in three batches and coded as presence/absence of any KRAS mutation (primary predictor). Age at diagnosis was dichotomized into adults (18 years) or children (KRAS mutations between children and adults (logistic), with bAVM size (linear), or with time from diagnosis to hemorrhage (survival), censoring at treatment or last follow-up. Results: We analyzed data from 221 patients: median age at bAVM diagnosis was 20 years; 44% were diagnosed as children; 53% were female; and 56% were ruptured on presentation. Median bAVM diameter was 2.1 cm (IQR: 1.4 - 3.0). KRAS mutations were detected in 53% of samples. Childhood bAVMs were significantly more likely to harbor KRAS mutations than those diagnosed in adulthood (OR=2.20, 95% CI: 1.24 - 3.91, p=0.007). KRAS -mutant bAVMs tended to be larger than KRAS -wildtype bAVMs, but this did not reach significance (+0.29 cm, 95% CI: -0.03 - 0.62, p=0.08). No association was observed for time to hemorrhage (HR=1.31, 95% CI: 0.91 - 1.88, p=0.15). Conclusions: Somatic activating KRAS mutations are more prevalent in bAVMs diagnosed in childhood than adulthood. Further work is required to elucidate mechanisms of mutagenesis and bAVM progression, which may differ in children and adults.
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- 2023
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37. 350 A Comparison of Incidental and Symptomatic Unruptured Brain Arteriovenous Malformations in Children
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Alex Y. Lu, Ethan A. Winkler, Joseph Garcia, Kunal P. Raygor, Heather Fullerton, Christine Fox, Helen Kim, Kurtis Ian Auguste, Peter P. Sun, Steven Hetts, Michael T. Lawton, Adib Adnan Abla, and Nalin Gupta
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Surgery ,Neurology (clinical) - Published
- 2023
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38. 484 Predictors of Outcome Clusters for Anterior Circulation Mechanical Thrombectomy: An Unsupervised Machine Learning Analysis of Prospective Data
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Anant Naik, Joshua Catapano, Joelle Nicole Hartke, Stefan Wolfgang Koester, Ethan A. Winkler, Ashutosh Jadhav, Andrew F. Ducruet, and Felipe Albuquerque
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Surgery ,Neurology (clinical) - Published
- 2023
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39. A cross-species proteomic map reveals neoteny of human synapse development
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Li Wang, Kaifang Pang, Li Zhou, Arantxa Cebrián-Silla, Susana González-Granero, Shaohui Wang, Qiuli Bi, Matthew L. White, Brandon Ho, Jiani Li, Tao Li, Yonatan Perez, Eric J. Huang, Ethan A. Winkler, Mercedes F. Paredes, Rothem Kovner, Nenad Sestan, Alex A. Pollen, Pengyuan Liu, Jingjing Li, Xianhua Piao, José Manuel García-Verdugo, Arturo Alvarez-Buylla, Zhandong Liu, and Arnold R. Kriegstein
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The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here, we generated a cross-species proteomic map of synapse development in the human, macaque, and mouse neocortex. By tracking the changes of >1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we found that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that the human PSD matures about two to three times slower than other species and contains higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of the RhoGEF signaling in human neurons delays the morphological maturation of dendritic spines and the functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Together, our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.
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- 2022
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40. Comparison of Outcomes following Primary and Repeat Resection of Craniopharyngioma
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Alexander A Aabedi, Ethan A. Winkler, Jacob S. Young, Michael W. McDermott, Philip V. Theodosopoulos, and Ryan R L Phelps
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medicine.medical_specialty ,Clinical Sciences ,reoperation ,Clinical Research ,medicine ,Adjuvant therapy ,Survival rate ,Cancer ,Neurology & Neurosurgery ,Surgical approach ,business.industry ,Primary resection ,endonasal ,Evaluation of treatments and therapeutic interventions ,Repeat resection ,medicine.disease ,Craniopharyngioma ,Surgery ,Cohort ,maximal safe resection ,Patient Safety ,Neurology (clinical) ,Complication ,business ,craniopharyngioma ,6.4 Surgery ,transcranial - Abstract
Introduction The management of recurrent craniopharyngioma is complex with limited data to guide decision-making. Some reports suggest reoperation should be avoided due to an increased complication profile, while others have demonstrated that safe reoperation can be performed. For other types of skull base lesions, maximal safe resection followed by adjuvant therapy has replaced radical gross total resection due to the favorable morbidity profiles. Methods Seventy-one patients underwent resection over a 9-year period for craniopharyngioma and were retrospectively reviewed. Patients were separated into primary resection and reoperation cohorts and stratified by surgical approach (endonasal vs. cranial) and survival analyses were performed based on cohort and surgical approach. Results Fifty patients underwent primary resection, while 21 underwent reoperation for recurrence. Fifty endonasal transsphenoidal surgeries and 21 craniotomies were performed. Surgical approaches were similarly distributed across cohorts. Subtotal resection was achieved in 83% of all cases. There were no differences in extent of resection, visual outcomes, subsequent neuroendocrine function, and complications across cohorts and surgical approaches. The median time to recurrence was 87 months overall, and there were no differences by cohort and approach. The 5-year survival rate was 81.1% after reoperation versus 93.2% after primary resection. Conclusion Compared with primary resection, reoperation for craniopharyngioma recurrence is associated with similar functional and survival outcomes in light of individualized surgical approaches. Maximal safe resection followed by adjuvant radiotherapy for residual tumor likely preserves vision and endocrine function without sacrificing overall patient survival.
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- 2021
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41. Intraventricular Tissue Plasminogen Activator and Shunt Dependency in Aneurysmal Subarachnoid Hemorrhage
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Mark A, Pacult, Joshua S, Catapano, Kavelin, Rumalla, Ethan A, Winkler, Christopher S, Graffeo, Visish M, Srinivasan, Ashutosh P, Jadhav, Andrew F, Ducruet, Felipe C, Albuquerque, and Michael T, Lawton
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Surgery ,Neurology (clinical) - Published
- 2023
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42. Tropism of SARS-CoV-2 for human cortical astrocytes
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Madeline G. Andrews, Tanzila Mukhtar, Ugomma C. Eze, Camille R. Simoneau, Jayden Ross, Neelroop Parikshak, Shaohui Wang, Li Zhou, Mark Koontz, Dmitry Velmeshev, Clara-Vita Siebert, Kaila M. Gemenes, Takako Tabata, Yonatan Perez, Li Wang, Mohammed A. Mostajo-Radji, Martina de Majo, Kevin C. Donohue, David Shin, Jahan Salma, Alex A. Pollen, Tomasz J. Nowakowski, Erik Ullian, G. Renuka Kumar, Ethan A. Winkler, Elizabeth E. Crouch, Melanie Ott, and Arnold R. Kriegstein
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1.1 Normal biological development and functioning ,Primary Cell Culture ,Vaccine Related ,Clinical Research ,Underpinning research ,Biodefense ,2.1 Biological and endogenous factors ,Humans ,Aetiology ,Lung ,Cerebral Cortex ,SARS-CoV-2 tropism ,Multidisciplinary ,SARS-CoV-2 ,Prevention ,Neurosciences ,Pneumonia ,Stem Cell Research ,Organoids ,Viral Tropism ,Emerging Infectious Diseases ,Infectious Diseases ,astrocyte reactivity ,Astrocytes ,Pneumonia & Influenza ,Angiotensin-Converting Enzyme 2 ,organoid models - Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.
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- 2022
43. Author Correction: Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
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Robert D. Bell, Ethan A. Winkler, Itender Singh, Abhay P. Sagare, Rashid Deane, Zhenhua Wu, David M. Holtzman, Christer Betsholtz, Annika Armulik, Jan Sallstrom, Bradford C. Berk, and Berislav V. Zlokovic
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Multidisciplinary - Published
- 2023
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44. The VEBAS score: a practical scoring system for intracranial dural arteriovenous fistula obliteration
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Andrea Becerril-Gaitan, Dale Ding, Natasha Ironside, Thomas J Buell, Akash P Kansagra, Giuseppe Lanzino, Waleed Brinjikji, Louis Kim, Michael R Levitt, Isaac Josh Abecassis, Diederik Bulters, Andrew Durnford, W Christopher Fox, Spiros Blackburn, Peng Roc Chen, Adam J Polifka, Dimitri Laurent, Bradley Gross, Minako Hayakawa, Colin Derdeyn, Sepideh Amin-Hanjani, Ali Alaraj, J Marc C van Dijk, Adriaan R E Potgieser, Robert M Starke, Eric C Peterson, Junichiro Satomi, Yoshiteru Tada, Adib A Abla, Ethan A Winkler, Rose Du, Pui Man Rosalind Lai, Gregory J Zipfel, Ching-Jen Chen, and Jason P Sheehan
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Surgery ,Neurology (clinical) ,General Medicine - Abstract
BackgroundTools 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.MethodsPatients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC.ResultsA total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (ConclusionThe VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.
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- 2023
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45. 483 Partial Treatment as a Risk Factor in Up-Conversion of Type 1 dAVFs
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Erin Walker, Anja I. Srienc, Ridhima Rao Guniganti, Waleed Brinjikji, Ching-Jen Chen, Isaac Josh Abecassis, Michael Robert Levitt, Andrew Durnford, Adam J. Polifka, Colin P. Derdeyn, Edgar A. Samaniego, Amanda M. Kwasnicki, Ali Alaraj, Adriaan R.E. Potgieser, Samir Sur, Yoshiteru Tada, Ethan A. Winkler, Rosalind Lai, Rose Du, Adib Adnan Abla, Junichiro Satomi, Robert M. Starke, Marc C. Van Dijk, Sepideh Amin-Hanjani, Minako Hayakawa, Bradley A. Gross, William C. Fox, Diederik Butlers, Louis J. Kim, Jason P. Sheehan, Giuseppe Lanzino, Joshua William Osbun, and Gregory J. Zipfel
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Surgery ,Neurology (clinical) - Published
- 2023
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46. 475 Local Conditional Induction of Brain Arteriovenous Malformations in Alk1-Inducible Knock-Out Mice
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Lea Scherschinski, Chul Han, Ethan A. Winkler, Peter Vajkoczy, Michael T. Lawton, and S. Paul Oh
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Surgery ,Neurology (clinical) - Published
- 2023
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47. 196 Increased Hemorrhage Risk With Brain AVM-Associated Aneurysms in Children
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Alex Y. Lu, Ethan A. Winkler, Ramin Morshed, Nalin Gupta, and Adib Adnan Abla
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Surgery ,Neurology (clinical) - Published
- 2023
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48. 385 A Cell Resolution Atlas of the Human Cerebrovasculature Reveals Angiogenic and Inflammatory Cell Programs in Arteriovenous Malformations
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Ethan A. Winkler, Chang Kim, Jayden Ross, Joseph Garcia, Eugene Gil, Irene Oh, Lindsay Chen, David Wu, Joshua Catapano, Kunal P. Raygor, Kazim Narsinh, Helen Kim, Shantel Weinsheimer, Daniel Cooke, Brian Patrick Walcott, Michael T. Lawton, Nalin Gupta, Berislav Zlokovic, Edward F. Chang, Adib Adnan Abla, Daniel A. Lim, and Tomasz Nowakowski
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Surgery ,Neurology (clinical) - Published
- 2023
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49. Total 1-year hospital cost of middle meningeal artery embolization compared to surgery for chronic subdural hematomas: a propensity-adjusted analysis
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Joshua S Catapano, Stefan W Koester, Visish M Srinivasan, Kavelin Rumalla, Jacob F Baranoski, Caleb Rutledge, Tyler S Cole, Ethan A Winkler, Michael T Lawton, Ashutosh P Jadhav, Andrew F Ducruet, and Felipe C Albuquerque
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Hematoma, Subdural, Chronic ,Humans ,Surgery ,Neurology (clinical) ,General Medicine ,Hospital Costs ,Embolization, Therapeutic ,Meningeal Arteries ,Retrospective Studies - Abstract
BackgroundMiddle meningeal artery (MMA) embolization results in fewer treatment failures than surgical evacuation for chronic subdural hematomas (cSDHs). We compared the total 1-year hospital cost for MMA embolization versus surgical evacuation for patients with cSDH.MethodsData for patients who presented with cSDHs from January 1, 2018, through May 31, 2020, were retrospectively reviewed. Patients were grouped by initial treatment (surgery vs MMA embolization), and total hospital cost was obtained. A propensity-adjusted analysis was performed. The primary outcome was difference in mean hospital cost between treatments.ResultsOf 170 patients, 48 (28%) underwent embolization and 122 (72%) underwent surgery. cSDHs were larger in the surgical (20.5 (6.7) mm) than in the embolization group (16.9 (4.6) mm; PConclusionsMMA embolization is associated with decreased total hospital cost compared with surgery for cSDHs. This lower cost is directly related to the decreased need for additional treatment interventions.
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- 2021
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50. Endovascular embolization versus surgical clipping in a single surgeon series of basilar artery aneurysms: a complementary approach in the endovascular era
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Ethan A. Winkler, Roberto Rodriguez Rubio, Mitchel S. Berger, Anthony T. Lee, S. Andrew Josephson, Kunal P. Raygor, John K. Yue, Adib A. Abla, Daniel M.S. Raper, and W. Caleb Rutledge
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Adult ,Male ,medicine.medical_specialty ,Original Article - Vascular Neurosurgery - Aneurysm ,Microsurgery ,medicine.medical_treatment ,Clinical Sciences ,Outcomes ,Aneurysm ,Postoperative Complications ,medicine.artery ,medicine ,Basilar artery ,Humans ,Endovascular coil embolization ,Embolization ,cardiovascular diseases ,Neuroradiology ,Aged ,Neurology & Neurosurgery ,medicine.diagnostic_test ,business.industry ,Microsurgical clipping ,Endovascular Procedures ,Neurosciences ,Interventional radiology ,Intracranial Aneurysm ,Middle Aged ,medicine.disease ,Surgical Instruments ,Embolization, Therapeutic ,Surgery ,Basilar Artery ,Cohort ,cardiovascular system ,Stents ,Neurology (clinical) ,Neurosurgery ,business - Abstract
Background Currently, most basilar artery aneurysms (BAAs) are treated endovascularly. Surgery remains an appropriate therapy for a subset of all intracranial aneurysms. Whether open microsurgery would be required or utilized, and to what extent, for BAAs treated by a surgeon who performs both endovascular and open procedures has not been reported. Methods Retrospective analysis of prospectively maintained, single-surgeon series of BAAs treated with endovascular or open surgery from the first 5 years of practice. Results Forty-two procedures were performed in 34 patients to treat BAAs—including aneurysms arising from basilar artery apex, trunk, and perforators. Unruptured BAAs accounted for 35/42 cases (83.3%), and the mean aneurysm diameter was 8.4 ± 5.4 mm. Endovascular coiling—including stent-assisted coiling—accounted for 26/42 (61.9%) treatments and led to complete obliteration in 76.9% of cases. Four patients in the endovascular cohort required re-treatment. Surgical clip reconstruction accounted for 16/42 (38.1%) treatments and led to complete obliteration in 88.5% of cases. Good neurologic outcome (mRS ≤ 2) was achieved in 88.5% and 75.0% of patients in endovascular and open surgical cohorts, respectively (p = 0.40). Univariate logistic regression analysis demonstrated that advanced age (OR 1.11[95% CI 1.01–1.23]) or peri-procedural adverse event (OR 85.0 [95% CI 6.5–118.9]), but not treatment modality (OR 0.39[95% CI 0.08–2.04]), was the predictor of poor neurologic outcome. Conclusions Complementary implementation of both endovascular and open surgery facilitates individualized treatment planning of BAAs. By leveraging strengths of both techniques, equivalent clinical outcomes and technical proficiency may be achieved with both modalities.
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- 2021
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