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1.
Interv Neuroradiol ; : 15910199241232726, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38389309

RESUMEN

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. CONCLUSION: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

2.
J Neurointerv Surg ; 16(4): 425-428, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-37258227

RESUMEN

The last 10 years have seen a major shift in management of large vessel ischemic stroke with changes towards ever-expanding use of reperfusion therapies (intravenous thrombolysis and mechanical thrombectomy). These strategies 'open the door' to acute therapeutics for ischemic tissue, and we should investigate novel therapeutic approaches to enhance survival of recently reperfused brain. Key insights into new approaches have been provided through translational research models and preclinical paradigms, and through detailed research on ischemic mechanisms. Additional recent clinical trials offer exciting salvos into this new strategy of pairing reperfusion with neuroprotective therapy. This pairing strategy can be employed using drugs that have shown neuroprotective efficacy; neurointerventionalists can administer these during or immediately after reperfusion therapy. This represents a crucial moment when we emphasize reperfusion, and have the technological capability along with the clinical trial experience to lead the way in multiprong approaches to stroke treatment.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Trombectomía , Resultado del Tratamiento , Fibrinolíticos/uso terapéutico
3.
Stroke ; 54(10): e465-e479, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37609846

RESUMEN

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.


Asunto(s)
Enfermedad de Moyamoya , Accidente Cerebrovascular , Estados Unidos/epidemiología , Humanos , Adulto , American Heart Association , Enfermedad de Moyamoya/diagnóstico , Enfermedad de Moyamoya/epidemiología , Enfermedad de Moyamoya/terapia , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/epidemiología
5.
BMC Neurol ; 23(1): 214, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37280551

RESUMEN

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery. METHODS: At the University of Kentucky Center for Advanced Translational Stroke Sciences, the BACTRAC tissue registry (clinicaltrials.gov; NCT03153683) of human biospecimens acquired during ELVO stroke by MT is utilized for research. Clinical data are collected on each enrolled subject who meets inclusion criteria. Blood samples obtained during thrombectomy were sent to Olink Proteomics for proteomic expression values. Montreal Cognitive Assessments (MoCA) were evaluated with categorical variables using ANOVA and t-tests, and continuous variables using Pearson correlations. RESULTS: There were n = 52 subjects with discharge MoCA scores and n = 28 subjects with 90-day MoCA scores. Several systemic and intracranial proteins were identified as having significant correlations to discharge MoCA scores as well as 90-day MoCA scores. Highlighted proteins included s-DPP4, CCL11, IGFBP3, DNER, NRP1, MCP1, and COMP. CONCLUSION: We set out to identify proteomic predictors and potential therapeutic targets related to cognitive outcomes in ELVO subjects undergoing MT. Here, we identify several proteins which predicted MoCA after MT, which may serve as therapeutic targets to lessen post-stroke cognitive decline.


Asunto(s)
Arteriopatías Oclusivas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Proteómica , Resultado del Tratamiento , Trombectomía , Estudios Retrospectivos
6.
Methods Mol Biol ; 2616: 47-54, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36715927

RESUMEN

Moyamoya is a cerebrovascular condition that predisposes affected patients to stroke and is characterized as the progressive stenosis of the internal carotid artery (ICA) and compensatory development of collaterals at the base of the brain. Patients with moyamoya syndrome also present with comorbidities such as various autoimmune diseases and coagulopathies. We developed a surgical method using micro-coils to induce ICA-specific stenosis in mice, which induces moyamoya-like vasculopathies. An advantage of this surgical model of hypoperfusion is that it can be combined with other comorbid models to investigate pathologies associated with moyamoya syndrome.


Asunto(s)
Estenosis Carotídea , Enfermedad de Moyamoya , Accidente Cerebrovascular , Ratones , Animales , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/cirugía , Enfermedad de Moyamoya/patología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/cirugía , Constricción Patológica/complicaciones , Encéfalo/patología , Modelos Animales de Enfermedad
7.
Methods Mol Biol ; 2616: 391-402, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36715948

RESUMEN

The majority of strokes, approximately 87%, are ischemic in etiology with the remaining hemorrhagic in origin. Emergent large vessel occlusions (ELVOs) are a subtype of ischemic stroke accounting for approximately 30-40% of acute large vessel blockages. Treatment for ELVOs focuses on recanalization of the occluded vessel by time-sensitive administration of tissue plasminogen activator (tPA) or thrombus removal using mechanical thrombectomy. Although a great deal of time and resources have focused on translational stroke research, little progress has been made in the area of identifying additional new treatments for stroke. Translational limitations include difficulty simulating human comorbid conditions in animal models, as well as the temporal nature of stroke pathology. The Blood And Clot Thrombectomy Registry And Collaboration represents an ongoing tissue registry for thrombectomy patients and includes collection of intracranial arterial blood, systemic arterial blood, thrombi, as well as a series of clinical and radiographic data points for analysis. This chapter will explore the methodologies employed and results obtained from studying BACTRAC-derived human biological specimens and how they can inform translational experimental design in animal studies.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Trombosis , Animales , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Isquemia Encefálica/terapia , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/tratamiento farmacológico , Trombectomía/efectos adversos , Trombectomía/métodos , Trombosis/etiología , Trombosis/terapia , Resultado del Tratamiento
8.
J Neurointerv Surg ; 15(1): 5-7, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36396432

RESUMEN

BACKGROUND: The aim of this article is to outline a position statement on pregnancy and parental leave for physicians practicing neurointerventional surgery. METHODS: We performed a structured literature review regarding parental leave policies in neurointerventional surgery and related fields. The recommendations resulted from discussion among the authors, and additional input from the Women in NeuroIntervention Committee, the full Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee, and the SNIS Board of Directors. RESULTS: Some aspects of workplace safety during pregnancy are regulated by the US Nuclear Regulatory Commission. Other aspects of the workplace and reasonable job accommodations are legally governed by the Family and Medical Leave Act of 1993, the Affordable Care Act of 2010 and the Fair Labor Standards Act of 1938, Americans with Disabilities Act of 1990, Title IX of the Education Amendments of 1972, Title VII of the Civil Rights Act of 1964 as well as rights and protections put forth by the Occupational Safety and Health Administration as part of the United States Department of Labor. Family friendly policies have been associated not only with improved job satisfaction but also with improved parental and infant outcomes. Secondary effects of such accommodations are to increase the number of women within the specialty. CONCLUSIONS: SNIS supports a physician's ambition to have a family as well as start, develop, and maintain a career in neurointerventional surgery. Legal and regulatory mandates and family friendly workplace policies should be considered when institutions and individual practitioners approach the issue of childbearing in the context of a career in neurointerventional surgery.


Asunto(s)
Permiso Parental , Médicos , Embarazo , Femenino , Estados Unidos , Humanos , Patient Protection and Affordable Care Act , Satisfacción en el Trabajo , Padres
9.
J Neurointerv Surg ; 15(3): 248-254, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35292570

RESUMEN

BACKGROUND: The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale. METHODS: PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated. RESULTS: As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series. CONCLUSIONS: The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture. TRIAL REGISTRATION: NCT02186561.


Asunto(s)
Embolización Terapéutica , Aneurisma Intracraneal , Humanos , Angiografía Cerebral/métodos , Embolización Terapéutica/métodos , Estudios de Seguimiento , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Aneurisma Intracraneal/etiología , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento
10.
Transl Stroke Res ; 14(3): 283-296, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36109476

RESUMEN

Subarachnoid hemorrhage (SAH) is a major health burden that accounts for approximately 5% of all strokes. The most common cause of a non-traumatic SAH is the rupture of a cerebral aneurysm. The most common symptom associated with SAH is a headache, often described as "the worst headache of my life." Delayed cerebral ischemia (DCI) is a major factor associated with patient mortality following SAH and is often associated with SAH-induced cerebral vasospasm (CV). Cannabidiol (CBD) is emerging as a potential drug for many therapeutic purposes, including epilepsy, anxiety, and pain relief. We aim to review the potential use of CBD as a treatment option for post-SAH critically ill patients. Through a literature review, we evaluated the known pharmacology and physiological effects of CBD and correlated those with the pathophysiological outcomes associated with cerebral vasospasm following subarachnoid hemorrhage. Although overlap exists, data were formatted into three major categories: anti-inflammatory, vascular, and neuroprotective effects. Based on the amount of information known about the actions of CBD, we hypothesize the anti-inflammatory effects are likely to be the most promising therapeutic mechanism. However, its cardiovascular effects through calcium regulation and its neuroprotective effects against cell death, excitotoxicity, and oxidative stress are all plausible mechanisms by which post-SAH critically ill patients may benefit from both early and late intervention with CBD. More research is needed to better understand if and how CBD might affect neurological and vascular functions in the brain following injury such as subarachnoid hemorrhage.


Asunto(s)
Isquemia Encefálica , Cannabidiol , Fármacos Neuroprotectores , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Cannabidiol/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/etiología , Fármacos Neuroprotectores/uso terapéutico , Enfermedad Crítica , Isquemia Encefálica/tratamiento farmacológico , Cefalea/complicaciones
11.
Transl Stroke Res ; 14(6): 842-853, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36125734

RESUMEN

Ischemic stroke is a leading cause of death and disability. However, very few neuroprotective agents have shown promise for treatment of ischemic stroke in clinical trials, despite showing efficacy in many successful preclinical studies. This may be attributed, at least in part, to the incongruency between experimental animal stroke models used in preclinical studies and the manifestation of ischemic stroke in humans. Most often the human population selected for clinical trials are more diverse than the experimental model used in a preclinical study. For successful translation, it is critical to develop clinical trial designs that match the experimental animal model used in the preclinical study. This review aims to provide a comprehensive summary of commonly used animal models with clear correlates between rodent models used to study ischemic stroke and the clinical stroke pathologies with which they most closely align. By improving the correlation between preclinical studies and clinical trials, new neuroprotective agents and stroke therapies may be more accurately and efficiently identified.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Accidente Cerebrovascular , Animales , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Modelos Animales de Enfermedad , Isquemia Encefálica/complicaciones
12.
Surg Neurol Int ; 13: 494, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36447849

RESUMEN

Background: Cholesteatomas are growths of squamous epithelium that can form inside the middle ear and mastoid cavity and damage nearby structures causing hearing loss when located at the petrous apex. The primary goal of petrous apex cholesteatoma resection is gross total removal with tympanoplasty and canal-wall up or canal-wall down tympanomastoidectomy. At present, there is no definitive surgical approach supported by greater than level 4 evidence in the literature to date. Methods: A systematic review was conducted utilizing PubMed, Embase, and Scopus databases. Articles were screened and selected to be reviewed in full text. The articles that met inclusion criteria were reviewed for relevant data. Data analysis, means, and standard deviations were calculated using Microsoft Excel. Results: After screening, five articles were included in the systematic review. There were a total of eight pediatric patients with nine total cholesteatomas removed. Conductive hearing loss was the most common (77%) presenting symptom. Perforations were noted in seven ears (86%). Recurrence was noted in 50% of patients with an average recurrence rate of 3.5 years (SD = 1.73). Average length of follow-up was 32.6 months (SD = 21.7). Canal-wall up was the most utilized technique (60%) and there were zero noted surgical complications. Five of the seven (71%) patients that experienced hearing loss from perforation noted improved hearing. Conclusion: Due to its rarity, diagnostic evaluation and treatment can vary. Further, multi-institutional investigation is necessary to develop population-level management protocols for pediatric patients affected by petrous apex cholesteatomas.

13.
Neurochem Int ; 160: 105421, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36179808

RESUMEN

BACKGROUND: Stroke is a major cause of death and disability in the United States. Mechanical thrombectomy (MT) and tissue plasminogen activator are the current treatments for ischemic stroke, which have improved clinical outcomes. Despite these treatments, functional and cognitive deficits still occur demonstrating a need for predictive biomarkers for beneficial clinical outcomes which can be used as therapeutic targets for pharmacotherapy. The aim of this study compares the proteomic expression of systemic arterial blood collected at the time of MT to those from a matched cerebrovascular disease (CVD) control cohort. METHODS: The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683) collects and banks arterial blood, both distal and proximal to the thrombus, from ischemic stroke subjects undergoing MT. Arterial blood from patients undergoing a diagnostic angiogram was also collected and banked as CVD controls. Changes in cardiometabolic and inflammatory proteins between stroke and CVD controls were analyzed via Olink Proteomics. RESULTS: Proteins including ARTN, TWEAK, HGF, CCL28, FGF-5, CXCL9, TRANCE and GDNF were found to be decreased in stroke subjects when compared to CVD controls. CXCL1, CCL5, OSM, GP1BA, IL6, MMP-1, and CXCL5 were increased in stroke subjects when compared to CVD controls. These proteins were also significantly correlated to stroke outcome metrics such as NIHSS, infarct volume and MoCA scoring. CONCLUSION: Overall, acute stroke patients had an increase in inflammatory proteins with a decrease in trophic proteins systemically compared to matched CVD controls. Using our CVD controls, proteins of interest were directly compared to stroke patients with the same cerebrovascular risk factors instead of statistically controlling for comorbidities. The novel methodology of matching an arterial blood CVD control group to a stroke group, as well as controlling for age and comorbid status add to the literature on prognostic stroke biomarkers, which are specific targets for future therapeutics.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Factor Neurotrófico Derivado de la Línea Celular Glial , Humanos , Interleucina-6 , Metaloproteinasa 1 de la Matriz , Proteómica , Accidente Cerebrovascular/terapia , Activador de Tejido Plasminógeno , Resultado del Tratamiento , Estados Unidos
14.
J Neurosurg Case Lessons ; 3(8)2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36130547

RESUMEN

BACKGROUND: Access of the cavernous sinus (CS) via venous route from the inferior petrosal sinus (IPS) can sometimes be challenging during the treatment of carotid cavernous fistulas (CCF), largely because of anatomical variations, tortuosity, and/or difficult visualization of IPS given high retrograde flow through the fistulous connection. OBSERVATIONS: A 58-year-old male was transferred to our university hospital center after suspected diagnosis of CCF at another hospital by head computerized tomography-angiogram. His symptoms included three weeks of right eye pain that was later complicated by redness, diplopia, and blurry vision. In a diagnostic angiogram, separate contrast injections from the arterial side via internal carotid artery (ICA) and from the venous side via IPS did not reveal a connection point. Injecting contrast simultaneously from both arterial and venous ends resulted in visualization of a connection point allowing entry into the CS. LESSONS: Technique of simultaneous contrast injection from ICA and internal jugular vein is comparatively simple and saves an operator prolonged time and complexity of approach. In our case, it revealed fistulous point allowing navigation and completing the coiling.

15.
J Appl Clin Med Phys ; 23(8): e13669, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35748118

RESUMEN

PURPOSE: To demonstrate the clinical feasibility of a novel treatment planning algorithm via lightning dose optimizer (LDO) on Leksell Gamma Knife (LGK) GammaPlan with significantly faster planning times for stereotactic radiosurgery (SRS) of the complex and difficult arteriovenous malformations (AVMs) and pituitary adenomas. METHODS AND MATERIALS: After completing the in-house end-to-end phantom testing and independent dose verification of the recently upgraded LDO algorithm on GammaPlan using the MD Anderson's IROC anthropomorphic SRS head phantom irradiation credentialing, 20 previously treated GK-SRS patients (10 AVM, average volume 3.61 cm3 and 10 pituitary adenomas, average volume 0.86 cm3 ) who underwent manual forward planning on GammaPlan were retrospectively replanned via LDO. These pathologies were included because of the need for adequate dose delivery with organs at risk in very close proximity. LDO finds the target curvature boundary by well-formulated linear programing objectives and inversely optimizes the GK-SRS plan by isocenter placement, optimization, and sequencing. For identical target coverage, the LDO and original manual plans were compared for target conformity, gradient index, dose to critical organs, and surrounding normal brain. Additionally, various treatment delivery parameters, including beam-on time were recorded. RESULTS: For both patient cohorts, LDO provided similar target coverage with better dose conformity, tighter radiosurgical dose distribution with a lower value of gradient indices (all p < 0.001), and lower dose to critical organs. For AVMs, there was a significant reduction of normal brain V10Gy , V12Gy , and V14Gy by 4.74, 3.67, and 2.67 cm3 (all p < 0.001). LDO had twice the number of shots (p < 0.001), and longer beam-on time (p = 0.012) by a factor of 1.44. For pituitary adenomas, LDO provided systematically lower values of V10Gy , V12Gy , and V14Gy by 1.08, 0.86, and 0.68 cm3 (all p < 0.001), and lower maximum dose to optic pathway by 0.7 Gy (p = 0.005), but had almost twice the numbers of shots (p < 0.001) and increased beam-on time (p = 0.005) by a factor of 1.2. However, for both patient groups, the average planning time for the LDO was <5 min, compared to the estimated 30-90 min of manual planning times. CONCLUSION: GK-SRS treatment on Leksell Perfexion GammaPlan using the LDO provided highly conformal target coverage with a steep dose gradient, spared critical organs, and significantly reduced normal brain dose for complex targets at the cost of slightly higher treatment times. LDO generated high-quality treatment plans and could significantly reduce planning time. If available, the LDO algorithm is suggested for validation and clinical use for complex and difficult GK cases.


Asunto(s)
Malformaciones Arteriovenosas , Relámpago , Neoplasias Hipofisarias , Radiocirugia , Humanos , Neoplasias Hipofisarias/cirugía , Radiocirugia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Retrospectivos
16.
J Neurosurg ; 137(6): 1676-1686, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-35426830

RESUMEN

OBJECTIVE: There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS: Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS: Ten adults (mean ± SD [range] age 35 ± 15 [22-62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%-98%) and 90% (95% CI 56%-100%) of patients demonstrated > 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%-96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [-11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%-100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS: For the first time, to the authors' knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen. Clinical trial registration no.: NCT02819479 (ClinicalTrials.gov).


Asunto(s)
Neoplasias Encefálicas , Traumatismos por Radiación , Radiocirugia , Adulto , Humanos , Adulto Joven , Persona de Mediana Edad , Bevacizumab/uso terapéutico , Estudios Prospectivos , Traumatismos por Radiación/etiología , Encéfalo/patología , Radiocirugia/métodos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Necrosis/etiología , Edema/tratamiento farmacológico , Esteroides , Cefalea/etiología
17.
Stroke ; 53(5): e204-e217, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35343235

RESUMEN

Patients with premorbid disability or dementia have generally been excluded from randomized controlled trials of reperfusion therapies such as thrombolysis and endovascular therapy for acute ischemic stroke. Consequently, stroke physicians face treatment dilemmas in caring for such patients. In this scientific statement, we review the literature on acute ischemic stroke in patients with premorbid disability or dementia and propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of premorbid disability or dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies have also helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have helped demonstrate the comparable safety of endovascular therapy in patients with premorbid disability or dementia and in those without, complementing similar data on thrombolysis. These data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.


Asunto(s)
Demencia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , American Heart Association , Demencia/complicaciones , Demencia/epidemiología , Demencia/terapia , Humanos , Accidente Cerebrovascular/epidemiología , Terapia Trombolítica , Estados Unidos
18.
Brain Behav Immun Health ; 20: 100422, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35141572

RESUMEN

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke. METHODS: The Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N â€‹= â€‹61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes. RESULTS: The 61 subjects studied were broken into three categories: normal weight (BMI 18.5-24.9) which contained 19 subjects, overweight (BMI 25-30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p â€‹= â€‹0.041 and p â€‹= â€‹0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p â€‹= â€‹0.01 and p â€‹= â€‹0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p â€‹= â€‹0.013 and p â€‹= â€‹0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p â€‹= â€‹0.053 and p â€‹= â€‹0.032, respectively. CONCLUSIONS: When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

19.
J Clin Neurosci ; 97: 7-11, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35026606

RESUMEN

Ventriculostomy placement is a life-saving procedure. Our aim was to determine the predictors of inaccurate placement, our infection and hemorrhage rate. This was a retrospective study of EVD placements between January - November 2019. Data related to hemorrhage, infection and catheter misplacement were collected. Univariate and multivariate analyses of predictors of suboptimal catheter placement were performed. 131 consecutive patients underwent freehand EVD placement. The indications were subarachnoid hemorrhage in 36 (27.5%) patients, hemorrhagic stroke in 36 (27.5%), and trauma in 32 (24.4%) patients. Nine patients (6.8%) had culture-proven CSF bacterial infection. Sixteen (12.2%) patients developed small tract hemorrhage, while 8 (6.1%) patients developed large intraparenchymal hemorrhage. There was no correlation between tract hemorrhage or large hemorrhage with the use of antiplatelet or anticoagulation medicines on presentation, diagnosis or Kakarla grade. Trauma diagnosis (odds ratio 2.59, p-value 0.05), left side of EVD placement (odds ratio 2.84, p-value 0.03), increasing midline shift (odds ratio 1.09, p-value 0.03), and lower bicaudate index (odds ratio 0.56, p-value 0.02) were all predictors of Kakarla grade 3 suboptimal placement. When Kakarla grade 2 and 3 were combined, similar results were obtained except that midline shift was no longer statistically significant. The multivariable regression model predicting Kakarla 3 suboptimal placement revealed that low bicaudate index and left sided EVD were predictors of misplaced EVD.


Asunto(s)
Drenaje , Hemorragia Subaracnoidea , Catéteres , Drenaje/efectos adversos , Drenaje/métodos , Humanos , Estudios Retrospectivos , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/cirugía , Ventriculostomía/efectos adversos , Ventriculostomía/métodos
20.
World Neurosurg ; 158: e317-e322, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34728392

RESUMEN

BACKGROUND: Ischemic stroke is a prevalent, devastating disease with high morbidity and mortality. Despite extensive research using animal models, significant gaps remain in understanding the pathological processes in human stroke. We previously developed a tissue bank to analyze the blood immediately proximal and distal to an intracranial thrombus in patients undergoing mechanical thrombectomy (ClinicalTrials.gov identifier, NCT03153683). Our goal for the present project was to evaluate the blood gas changes and acid/base balance during stroke and determine how vascular collateralization affects these changes. METHODS: We analyzed the blood samples and computed tomography angiography collateral scores from the first 62 patients in the BACTRAC (Blood and Clot Thrombectomy Registry and Collaboration) registry. The bicarbonate, partial pressure of oxygen, and partial pressure of carbon dioxide (pCO2) values of the intracranial (distal) and systemic (proximal) arterial blood relative to the occlusive thrombus were analyzed. Analysis of the group differences in systemic and intracranial blood gas values was also performed. RESULTS: The partial pressure of oxygen, pCO2, and bicarbonate levels were all significantly higher in the systemic blood than in the intracranial blood (P < 0.001 for all) at thrombectomy. Collateralization did not significantly affect the distal blood gas values. Compared with the female patients, the male patients had had higher systemic pCO2 values (39.8 vs. 36.6 mm Hg; P = 0.0065) and lower systemic and intracranial pH values (7.351 vs. 7.392; P = 0.0047). CONCLUSIONS: The arterial blood gases differed immediately proximal and distal to thrombi in large vessel occlusive stroke. Although vascular collateralization did not appear to affect the blood gas changes, some blood gas values differed between men and women. The changes in bicarbonate and pCO2 suggested a compensatory acid-base process occurring at the time of infarction.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Trombosis , Animales , Bicarbonatos , Femenino , Gases , Humanos , Infarto , Masculino , Oxígeno , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Trombosis/patología , Resultado del Tratamiento
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