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1.
Brain Sci ; 14(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672043

RESUMO

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.

2.
Neurosurg Rev ; 47(1): 190, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658446

RESUMO

OBJECTIVE: We assessed types of cadaveric head and brain tissue specimen preparations that are used in a high throughput neurosurgical research laboratory to determine optimal preparation methods for neurosurgical anatomical research, education, and training. METHODS: Cadaveric specimens (N = 112) prepared using different preservation and vascular injection methods were imaged, dissected, and graded by 11 neurosurgeons using a 21-point scale. We assessed the quality of tissue and preservation in both the anterior and posterior circulations. Tissue quality was evaluated using a 9-point magnetic resonance imaging (MRI) scale. RESULTS: Formalin-fixed specimens yielded the highest scores for assessment (mean ± SD [17.0 ± 2.8]) vs. formalin-flushed (17.0 ± 3.6) and MRI (6.9 ± 2.0). Cadaver assessment and MRI scores were positively correlated (P < 0.001, R2 0.60). Analysis showed significant associations between cadaver assessment scores and specific variables: nonformalin fixation (ß = -3.3), preservation within ≤72 h of death (ß = 1.8), and MRI quality score (ß = 0.7). Formalin-fixed specimens exhibited greater hardness than formalin-flushed and nonformalin-fixed specimens (P ≤ 0.006). Neurosurgeons preferred formalin-flushed specimens injected with colored latex. CONCLUSION: For better-quality specimens for neurosurgical education and training, formalin preservation within ≤72 h of death was preferable, as was injection with colored latex. Formalin-flushed specimens more closely resembled live brain parenchyma. Assessment scores were lower for preparation techniques performed > 72 h postmortem and for nonformalin preservation solutions. The positive correlation between cadaver assessment scores and our novel MRI score indicates that donation organizations and institutional buyers should incorporate MRI as a screening tool for the selection of high-quality specimens.


Assuntos
Encéfalo , Cadáver , Imageamento por Ressonância Magnética , Neurocirurgia , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neurocirurgia/educação , Procedimentos Neurocirúrgicos/métodos
3.
Res Pract Thromb Haemost ; 8(2): 102347, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38496712

RESUMO

Background: Recent literature has demonstrated remarkable heterogeneity in the composition of acute ischemic stroke (AIS) emboli, which may impact susceptibility to therapy. Objectives: In this study, we explored differences in proteomic composition of retrieved embolic material from patients with stroke with and without atrial fibrillation (AF) (AF+ and AF-, respectively). Methods: The full proteome of retrieved thromboembolic material from 24 patients with AIS was obtained by mass spectrometry. Known marker proteins were assigned groups representing broad classes of embolus components: red blood cells, platelets, neutrophils, eosinophils, histones, complement, and other clotting-associated proteins (eg, fibrinogen). Relative protein abundances were compared between AF+ and AF- samples. Functional implications of differences were explored with gene set enrichment analysis and Gene Ontology enrichment analysis and visualization tool. Results: One hundred sixty-six proteins were differentially expressed between AF+ and AF- specimens. Eight out of the 15 neutrophil proteins (P < .05; fold change, >2) and 4 of the 14 histone proteins were significantly enriched in AF+ emboli (P < .05; fold change, >2). Gene set enrichment analysis revealed a significant representation of proteins from published neutrophil extracellular trap (NET) proteomic gene sets. The most significantly represented functional Gene Ontology pathways in patients with AF involved neutrophil activation and degranulation (P < 1 × 10-7). Conclusion: The present analysis suggests enrichment of NETs in emboli of patients with stroke and AF. NETs are a significant though understudied structural component of thrombi. This work suggests not only unique stroke biology in AF but also potential therapeutic targets for AIS in this population.

4.
Neurosurg Rev ; 47(1): 133, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556597

RESUMO

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.


Assuntos
Malformações Arteriovenosas , Bibliometria , Humanos , Fatores de Risco , Publicações , Sistema Nervoso Central
5.
Neurosurg Rev ; 47(1): 79, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353750

RESUMO

Decompressive hemicraniectomy (DHC) is a critical procedure used to alleviate elevated intracranial pressure (ICP) in emergent situations. It is typically performed to create space for the swelling brain and to prevent dangerous and potentially fatal increases in ICP. DHC is indicated for pathologies ranging from MCA stroke to traumatic subarachnoid hemorrhage-essentially any cause of refractory brain swelling and elevated ICPs. Scalp incisions for opening and closing the soft tissues during DHC are crucial to achieve optimal outcomes by promoting proper wound healing and minimizing surgical site infections (SSIs). Though the reverse question mark (RQM) scalp incision has gained significant traction within neurosurgical practice, alternatives-including the retroauricular (RA) and Kempe incisions-have been proposed. As choice of technique can impact postoperative outcomes and complications, we sought to compare outcomes associated with different scalp incision techniques used during DHC. We queried three databases according to PRISMA guidelines in order to identify studies comparing outcomes between the RQM versus "alternative" scalp incision techniques for DHC. Our primary outcome of interest in the present study was postoperative wound infection rates according to scalp incision type. Secondary outcomes included estimated blood loss (EBL) and operative duration. We identified seven studies eligible for inclusion in the formal meta-analysis. The traditional RQM technique shortened operative times by 36.56 min, on average. Additionally, mean EBL was significantly lower when the RQM scalp incision was used. Postoperatively, there was no significant association between DHC incision type and mean intensive care unit (ICU) length of stay (LOS), nor was there a significant difference in predisposition to developing wound complications or infections between the RQM and retroauricular/Kempe incision cohorts. Superficial temporal artery (STA) preservation and reoperation rates were collected but could not be analyzed due to insufficient number of studies reporting these outcomes. Our meta-analysis suggests that there is no significant difference between scalp incision techniques as they relate to surgical site infection and wound complications. At present, it appears that outcomes following DHC can be improved by ensuring that the bone flap is large enough to enable sufficient cerebral expansion and decompression of the temporal lobe, the latter of which is of particular importance. Although previous studies have suggested that there are several advantages to performing alternative scalp incision techniques during DHC, the present study (which is to our knowledge the first to meta-analyze the literature on outcomes in DHC by scalp incision type) does not support these findings. As such, further investigations in the form of prospective trials with high statistical power are merited.


Assuntos
Edema Encefálico , Couro Cabeludo , Humanos , Couro Cabeludo/cirurgia , Estudos Prospectivos , Infecção da Ferida Cirúrgica , Encéfalo
6.
J Neurol Surg B Skull Base ; 85(1): 95-105, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38327513

RESUMO

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

7.
Neurosurg Focus ; 56(1): E18, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163353

RESUMO

OBJECTIVE: Extended reality (XR) systems, including augmented reality (AR), virtual reality (VR), and mixed reality, have rapidly emerged as new technologies capable of changing the way neurosurgeons prepare for cases. Thus, the authors sought to evaluate the perspectives of neurosurgical trainees on the integration of these technologies into neurosurgical education. METHODS: A 20-question cross-sectional survey was administered to neurosurgical residents and fellows to evaluate perceptions of the use of XR in neurosurgical training. Respondents evaluated each statement using a modified Likert scale (1-5). RESULTS: One hundred sixteen responses were recorded, with 59.5% of participants completing more than 90% of the questions. Approximately 59% of participants reported having institutional access to XR technologies. The majority of XR users (72%) believed it was effective for simulating surgical situations, compared with only 41% for those who did not have access to XR. Most respondents (61%) agreed that XR could become a standard in neurosurgical education and a cost-effective training tool (60%). Creating patient-specific anatomical XR models was considered relatively easy by 56% of respondents. Those with XR access reported finding it easier to create intraoperative models (58%) than those without access. A significant percentage (79%) agreed on the need for technical skill training outside the operating room (OR), especially among those without XR access (82%). There was general agreement (60%) regarding the specific need for XR. XR was perceived as effectively simulating stress in the OR. Regarding clinical outcomes, 61% believed XR improved efficiency and safety and 48% agreed it enhanced resection margins. Major barriers to XR integration included lack of ample training hours and/or time to use XR amid daily clinical obligations (63%). CONCLUSIONS: The data presented in this study indicate that there is broad agreement among neurosurgical trainees that XR holds potential as a training modality in neurosurgical education. Moreover, trainees who have access to XR technologies tend to hold more positive perceptions regarding the benefits of XR in their training. This finding suggests that the availability of XR resources can positively influence trainees' attitudes and beliefs regarding the utility of these technologies in their education and training.


Assuntos
Realidade Aumentada , Realidade Virtual , Humanos , Estudos Transversais , Inquéritos e Questionários , Neurocirurgiões
8.
J Thromb Haemost ; 22(5): 1410-1420, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38296159

RESUMO

BACKGROUND: Fibrin, von Willebrand factor, and extracellular DNA from neutrophil extracellular traps all contribute to acute ischemic stroke thrombus integrity. OBJECTIVES: In this study, we explored how the proteomic composition of retrieved thromboemboli relates to susceptibility to lysis with distinct thrombolytics. METHODS: Twenty-six retrieved stroke thromboemboli were portioned into 4 segments, with each subjected to 1 hour of in vitro lysis at 37 °C in 1 of 4 solutions: tissue plasminogen activator (tPA), tPA + von Willebrand factor-cleaving ADAMTS-13, tPA + DNA-cleaving deoxyribonuclease (DNase) I, and all 3 enzymes. Lysis, characterized by the percent change in prelysis and postlysis weight, was compared across the solutions and related to the corresponding abundance of proteins identified on mass spectrometry for each of the thromboemboli used in lysis. RESULTS: Solutions containing DNase resulted in approximately 3-fold greater thrombolysis than that with the standard-of-care tPA solution (post hoc Tukey, P < .01 for all). DNA content was directly related to lysis in solutions containing DNase (Spearman's ρ > 0.39 and P < .05 for all significant histones) and inversely related to lysis in solutions without DNase (Spearman's ρ < -0.40 and P < .05 for all significant histones). Functional analysis suggests distinct pathways associated with susceptibility to thrombolysis with tPA (platelet-mediated) or DNase (innate immune system-mediated). CONCLUSION: This study demonstrates synergy of DNase and tPA in thrombolysis of stroke emboli and points to DNase as a potential adjunct to our currently limited selection of thrombolytics in treating acute ischemic stroke.


Assuntos
DNA , Fibrinolíticos , Histonas , AVC Isquêmico , Ativador de Plasminogênio Tecidual , Humanos , AVC Isquêmico/tratamento farmacológico , DNA/metabolismo , Histonas/metabolismo , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Masculino , Idoso , Feminino , Terapia Trombolítica , Desoxirribonuclease I/metabolismo , Desoxirribonuclease I/uso terapêutico , Pessoa de Meia-Idade , Proteômica/métodos , Proteína ADAMTS13/genética , Proteína ADAMTS13/metabolismo , Armadilhas Extracelulares/metabolismo , Fibrinólise/efeitos dos fármacos , Fator de von Willebrand/metabolismo , Idoso de 80 Anos ou mais , Trombose/tratamento farmacológico
9.
J Cereb Blood Flow Metab ; 44(7): 1174-1183, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38241458

RESUMO

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Camundongos Knockout , Receptores de Calcitriol , Deficiência de Vitamina D , Vitamina D , Animais , Deficiência de Vitamina D/complicações , Aneurisma Intracraniano/etiologia , Camundongos , Aneurisma Roto/etiologia , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/deficiência , Vitamina D/uso terapêutico , Vitamina D/sangue , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Modelos Animais de Doenças , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia
10.
Hypertension ; 81(3): 572-581, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38164754

RESUMO

BACKGROUND: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. METHODS: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. RESULTS: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. CONCLUSIONS: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Camundongos , Animais , Aneurisma Intracraniano/prevenção & controle , Aneurisma Intracraniano/genética , Hemorragia Subaracnóidea/prevenção & controle , Aneurisma Roto/metabolismo , Receptores ErbB , RNA Mensageiro , Estresse do Retículo Endoplasmático , Inflamação
11.
J Cerebrovasc Endovasc Neurosurg ; 26(1): 11-22, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37828746

RESUMO

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of middle meningeal artery embolization in terms of both clinical and radiographic outcomes, when performed with different embolic agents. METHODS: A systematic literature review and meta-analysis was performed to evaluate the impact of embolic agents on outcomes for middle meningeal artery (MMA) embolization. The use of polyvinyl alcohol (PVA) with or without (±) coils, N-butyl cyanoacrylate (n-BCA) ± coils, and Onyx alone were separately evaluated. Primary outcome measures were recurrence, the need for surgical rescue and in-hospital periprocedural complications. RESULTS: Thirty-one studies were identified with a total of 1,134 patients, with 786 receiving PVA, 167 receiving n-BCA, and 181 patients receiving Onyx. There was no difference in the recurrence rate (5.5% for PVA, 4.5% for n-BCA, and 6.5% for Onyx, with P=0.71) or need for surgical rescue (5.0% for PVA, 4.0% for n-BCA, and 6.9% for Onyx, with P=0.89) based on the embolic agent. Procedural complications also did not differ between embolic agents (1.8% for PVA, 3.6% for n-BCA, and 1.6% for Onyx, with P=0.48). CONCLUSIONS: Rates of recurrence, need for surgical rescue, and periprocedural complication following MMA embolization are not impacted by the type of embolic agent utilized. Ongoing clinical trials may be used to further investigate these findings.

12.
Oper Neurosurg (Hagerstown) ; 26(3): 341-345, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37815226

RESUMO

BACKGROUND AND OBJECTIVES: Surgical simulation models in cranial neurosurgery are needed to allow affordable, accessible, and validated practice in resident education. Current bypass anastomosis practice models revolve around basic tube tying or complex animal and 3-dimensional models. This study sought to design and validate a 3-dimensional printed model for intracranial anastomosis training. METHODS: A computer-aided design (CAD) generic skull was uploaded into Meshmixer (v.3.5), and a 55-mm opening was created on the right side, mimicking a standard orbitozygomatic craniotomy. The model was rotated 15° upward and 35° left, before a 10-mm square frame was added 80-mm deep to the right orbit. The CAD model was uploaded to GrabCAD and printed using a J750 PolyJet 3D printer before being paired with a vascular anastomosis kit. The model was validated with standardized assessments of residents and attendings by simulating an "M2 to P2" bypass. The Rochester Bypass Training Score (RBTS) was created to assess bypass patency, back wall suturing, and suture quality. Postsimulation survey data regarding the realism and usefulness of the simulation were collected. RESULTS: Five junior residents (Postgraduate Year 1-4), 3 senior residents (Postgraduate Year 5-7), and 2 attendings were participated. The mean operative time in minutes was as follows: junior residents 78, senior residents 33, and attendings 50. The RBTS means were as follows: junior residents 2.4, senior residents 4.0, and attendings 5.0. Participants agreed that the model was realistic, useful for improving operative technique, and would increase comfort in bypass procedures. There are a few different printing options, varying in model infill and printing material used. For this experiment, a mix of Vero plastics were used totaling $309.09 per model; however, using the more common printing material polylactic acid brings the cost to $17.27 for a comparable model. CONCLUSION: This study presents an affordable, realistic, and educational intracranial vascular anastomosis simulator and introduces the RBTS for assessment.


Assuntos
Internato e Residência , Neurocirurgia , Animais , Humanos , Procedimentos Neurocirúrgicos/educação , Neurocirurgia/educação , Anastomose Cirúrgica/educação , Impressão Tridimensional
14.
Interv Neuroradiol ; : 15910199231221449, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38130106

RESUMO

BACKGROUND: Spontaneous intracranial hypotension is a debilitating neurological condition which can be caused by a cerebrospinal fluid-venous fistula. Transvenous embolization is a promising technique to provide minimally invasive yet durable treatment. METHODS: A retrospective single-center case series was performed on all patients who underwent transvenous embolization of a cerebrospinal fluid (CSF)-venous fistula. Clinical and radiographic parameters, including Bern score, were reported preoperatively and at 3-month follow-up. RESULTS: Six patients underwent embolization of a CSF-venous fistula. All fistulae were located in the thoracic spine and technical success was achieved in all cases. Three patients had symptom resolution, two had significant improvement, and one had stable symptoms on follow-up. The mean Bern score was 6.83 (SD = 1.47) preoperatively and 1.83 (SD = 1.64) postoperatively with a mean improvement in Bern score of 5.0 (SD = 1.9, p = 0.0013). CONCLUSIONS: CSF-venous fistulas are an increasingly recognized clinical entity which may be treated with transvenous embolization. This case series serves to further validate this technique and suggests it can be performed with similar outcomes in lower volume centers.

15.
AJNR Am J Neuroradiol ; 45(1): 22-29, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38123915

RESUMO

BACKGROUND AND PURPOSE: Perviousness is the differential attenuation on CT of an intracranial arterial occlusive thrombus before and after IV contrast administration. While perviousness/permeability has been shown to be related to various clinical outcomes and reflects histopathologic composition, it remains unclear whether perviousness is also associated with differences in proteomic composition. MATERIALS AND METHODS: Retrieved clots from 59 patients were evaluated with quantitative mass spectrometry. Proteomic differences between high-perviousness (≥11 HU) and low-perviousness (<11 HU) clots were investigated. Perviousness as a continuous variable was also correlated with protein abundance. Last, an ex vivo lysis assay was performed to investigate the differential susceptibility to tPA, deoxyribonuclease, and ADAMTS13 thrombolysis as a function of perviousness. RESULTS: In total, 2790 distinct proteins were identified. Thrombus perviousness was associated with distinct proteomic features, including depletion of the macrophage marker CD14 (P = .039, z = 1.176) and hemoglobin subunit ζ (P = .046, z = 1.68) in pervious clots. Additionally, proteins involved in platelet cytoskeleton remodeling (tropomyosin α-3-chain) and granule secretion/aggregation (synaptotagmin-like protein 4/FC region receptor II-a) were associated with increasing perviousness (P < .006), among numerous other proteins. Monocyte/macrophage-associated proteins (apoptosis-associated specklike protein containing a CARD/SAMHD1) were also depleted in pervious emboli (P < .002). Ex vivo lysis indicated that pervious clots were more susceptible to ADAMTS13-augmented tPA thrombolysis compared with impervious clots (P < .05), though without differences in deoxyribonuclease digestion. CONCLUSIONS: Thrombus perviousness is associated with complex proteomic features, including differential abundance of platelet-related proteins in highly permeable clots with monocyte/macrophage depletion. This association may help to explain why highly pervious thrombi were also found more susceptible to ADAMTS13-augmented thrombolysis.


Assuntos
Isquemia Encefálica , Trombose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , Acidente Vascular Cerebral/patologia , Proteômica , Trombose Intracraniana/patologia , Trombose/patologia , Terapia Trombolítica , Desoxirribonucleases , Isquemia Encefálica/patologia , Proteína ADAMTS13
16.
Neurosurg Rev ; 46(1): 220, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658996

RESUMO

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.


Assuntos
Doenças Autoimunes , Doença de Moyamoya , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Doença de Moyamoya/complicações , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/cirurgia , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Bases de Dados Factuais
17.
Surg Neurol Int ; 14: 265, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560569

RESUMO

Background: Extradural arteriovenous fistulas (AVFs) of the cervical spine are extremely rare, and typically manifest as slowly progressive myelopathy caused by mass effect. This is a unique case of extradural AVF of the cervical spine manifesting with purely radicular symptoms and treated endovascularly with coil and liquid embolization. Case Description: A 55-year-old woman presented with neck pain and right upper extremity radiculopathy persisting for 9 months. Imaging studies demonstrated an AVF spanning from C4-C6 with extension into the C5-C6 foramen supplied primarily from the deep cervical branch of the costocervical trunk. The patient underwent successful coil and liquid (Onyx) embolization. Six-week postoperatively, the patient's symptoms completely resolved and magnetic resonance imaging and angiographic imaging confirmed complete obliteration of the fistula. Conclusion: While extradural AVFs typically present with myelopathic symptoms, they may present with solely radicular symptoms and can be successfully treated endovascularly.

18.
J Neurosurg Pediatr ; 32(4): 437-446, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37410601

RESUMO

OBJECTIVE: While CSF diversion is highly effective at treating hydrocephalus, shunting is unfortunately associated with a very high revision rate. Studies have demonstrated that proximal catheter obstruction is a major cause of failure. A novel proximal access device was developed, and pilot testing was performed in a sheep model of hydrocephalus. METHODS: Hydrocephalus was induced in 8 sheep using a cisternal injection of 4 ml of 25% kaolin, and the sheep were randomized to either a standard ventricular catheter or a novel intraparenchymal stent (IPS). Both groups received identical valves and distal catheters. The novel device included a 3D-printed stainless steel port and a 6 × 40-mm covered peripheral vascular stent. Animals were euthanized for signs of hydrocephalus or at a time point of 2 months. MRI was performed to determine ventricular size. Time to failure and Evans indices were compared using the Wilcoxon rank-sum test. RESULTS: All 4 experimental devices were placed without difficulty into the right lateral ventricle. There was a trend toward longer survival in the experimental group (40 vs 26 days, p = 0.24). Within the IPS group, 3 of the 4 sheep did not experience clinical symptoms of shunt failure and had an average of 37% decrease in Evans index. While 3 of 4 traditional proximal catheters demonstrated debris within the inlet holes, there was no obstructive material found in the IPSs. CONCLUSIONS: An IPS was successfully used to treat hydrocephalus in a sheep model. While statistical significance was not achieved, there were clear benefits to using a stent, including a decreased clog rate and the ability to perform a percutaneous revision. Further testing is needed to ensure efficacy and safety prior to human application.


Assuntos
Hidrocefalia , Animais , Catéteres/efeitos adversos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Ventrículos Laterais , Procedimentos Neurocirúrgicos/efeitos adversos , Ovinos , Derivação Ventriculoperitoneal/efeitos adversos , Estudo de Prova de Conceito
20.
J Neurointerv Surg ; 15(12): 1264-1268, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36878687

RESUMO

BACKGROUND: Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition. METHODS: Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition. Presence (+) or absence (-) of HCAS on preintervention non-contrast head CT was then determined and correlated with thrombus protein signature with abundance of individual proteins calculated as a function HCAS status. RESULTS: 24 clots with 1797 distinct proteins in total were identified. 14 patients were HCAS(+) and 10 were HCAS(-). HCAS(+) were most significantly differentially abundant in actin cytoskeletal protein (P=0.002, Z=2.82), bleomycin hydrolase (P=0.007, Z=2.44), arachidonate 12-lipoxygenase (P=0.004, Z=2.60), and lysophospholipase D (P=0.007, Z=2.44), among other proteins; HCAS(-) clots were differentially enriched in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (P=0.0009, Z=3.11), tyrosine-protein kinase Fyn (P=0.002, Z=2.84), and several complement proteins (P<0.05, Z>1.71 for all), among numerous other proteins. Additionally, HCAS(-) thrombi were enriched in biological processes involved with plasma lipoprotein and protein-lipid remodeling/assembling, and lipoprotein metabolic processes (P<0.001), as well as cellular components including mitochondria (P<0.001). CONCLUSIONS: HCAS is reflective of distinct proteomic composition in AIS thrombus. These findings suggest that imaging can be used to identify mechanisms of clot formation or maintenance at the protein level, and might inform future research on thrombus biology and imaging characterization.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , AVC Isquêmico/complicações , Isquemia Encefálica/etiologia , Proteômica , Trombose/patologia , Acidente Vascular Cerebral/etiologia , Artérias Cerebrais/patologia , Tomografia Computadorizada por Raios X/métodos , Lipoproteínas , Trombectomia/métodos
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