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1.
J Stroke Cerebrovasc Dis ; 33(6): 107698, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531437

RESUMO

INTRODUCTION: The Zoom aspiration catheters harbor novel dimensions and construction to enhance trackability and deliverability. In addition, a beveled tip may improve thrombus interaction and aspiration force for a set inner diameter. This study evaluates their utility in medium and distal vessel occlusions. OBJECTIVE: To evaluate the safety and efficacy of Zoom 45 and 55 aspiration catheters in medium and distal vessel thrombectomy. METHODS: Patients treated for distal vessel occlusions via mechanical thrombectomy utilizing either the Zoom 45/55 catheter or a historical control catheter between 2021-2022 at two institutions were included in this study. Medium and distal occlusions were defined as any anterior or posterior cerebral artery branch as well as the M2-4 segment of the middle cerebral artery (MCA). Preprocedural, procedural, and postprocedural variables were obtained. RESULTS: Thirty-eight patients underwent thrombectomy with Zoom 45 or 55 catheters; four had multiple occluded vessels. Occlusion location included the M2 in 32 cases, M3-4 in 7 cases, A2 in 2 cases and P2 in 1 case. The mean number of passes per occlusion was 1.6 and overall successful reperfusion (TICI 2b or greater) was achieved in 84 % of cases. There were no symptomatic procedure-related complications such as perforation or post-procedural symptomatic ICH. Modified Rankin scores rates of 0-2, 3-5, and 6 at three months post-procedure were 35.7 %, 21.4 %, and 42.9 %, respectively. CONCLUSIONS: The Zoom beveled tip aspiration catheters are safe and effective for more challenging medium and distal vessel occlusions.


Assuntos
Desenho de Equipamento , Trombectomia , Humanos , Feminino , Masculino , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Trombectomia/instrumentação , Trombectomia/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Idoso de 80 Anos ou mais , Dispositivos de Acesso Vascular , Fatores de Risco , Catéteres
2.
Radiology ; 307(4): e222045, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37070990

RESUMO

Background Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited. Purpose To identify predictors of MMAE treatment failure for CSDH. Materials and Methods In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models were constructed to identify independent failure predictors, controlling for age, sex, concurrent surgical evacuation, midline shift, hematoma thickness, and pretreatment baseline antiplatelet and anticoagulation therapy. Results Overall, 530 patients (mean age, 71.9 years ± 12.8 [SD]; 386 men; 106 with bilateral lesions) underwent 636 MMAE procedures. At presentation, the median CSDH thickness was 15 mm and 31.3% (166 of 530) and 21.7% (115 of 530) of patients were receiving antiplatelet and anticoagulation medications, respectively. Clinical failure occurred in 36 of 530 patients (6.8%, over a median follow-up of 4.1 months) and radiographic failure occurred in 26.3% (137 of 522) of procedures. At multivariable analysis, independent predictors of clinical failure were pretreatment anticoagulation therapy (odds ratio [OR], 3.23; P = .007) and an MMA diameter less than 1.5 mm (OR, 2.52; P = .027), while liquid embolic agents were associated with nonfailure (OR, 0.32; P = .011). For radiographic failure, female sex (OR, 0.36; P = .001), concurrent surgical evacuation (OR, 0.43; P = .009), and a longer imaging follow-up time were associated with nonfailure. Conversely, MMA diameter less than 1.5 mm (OR, 1.7; P = .044), midline shift (OR, 1.1; P = .02), and superselective MMA catheterization (without targeting the main MMA trunk) (OR, 2; P = .029) were associated with radiographic failure. Sensitivity analyses retained these associations. Conclusion Multiple independent predictors of failure of MMAE treatment for chronic subdural hematomas were identified, with small diameter (<1.5 mm) being the only factor independently associated with both clinical and radiographic failures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chaudhary and Gemmete in this issue.


Assuntos
Embolização Terapêutica , Hematoma Subdural Crônico , Masculino , Humanos , Feminino , Idoso , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/terapia , Estudos Retrospectivos , Artérias Meníngeas/diagnóstico por imagem , Artérias Meníngeas/cirurgia , Embolização Terapêutica/métodos , Anticoagulantes
3.
Cell Mol Neurobiol ; 43(6): 2697-2711, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37046105

RESUMO

Intracranial aneurysms are reported to affect 2-5% of the population. Despite advances in the surgical management of this disease, diagnostic technologies have marginally improved and still rely on expensive or invasive imaging procedures. Currently, there is no blood-based test to detect cerebral aneurysm formation or quantify the risk of rupture. The aim of this review is to summarize current literature on the mechanism of aneurysm formation, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future blood-based test. Efforts should be focused on clinical-translational approaches to create an assay to screen for cerebral aneurysm presence and risk-stratify patients to allow for superior treatment timing and management. Cerebral Aneurysm Blood Test Considerations: There are multiple caveats to development of a putative blood test to detect cerebral aneurysm presence.


Assuntos
Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico , Proteômica , Inflamação
4.
Neurosurg Rev ; 46(1): 252, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37726558

RESUMO

Brainstem cavernous malformations (CMs) encompass up to 20% of all intracranial CMs and are considered more aggressive than cerebral CMs because of their high annual bleeding rates. Microsurgical resection remains the primary treatment modality for CMs, but long-term functional outcomes and complications are heterogenous in the literature. The authors performed a systematic review on brainstem CMs in 4 databases: PubMed, EMBASE, Cochrane library, and Google Scholar. We included studies that reported on the long-term functional outcomes and complications of brainstem CMs microsurgical resection. A meta-analysis was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search yielded 4781 results, of which 19 studies met our inclusion criteria. Microsurgery was performed on 940 patients (mean age 35 years, 46.9% females). Most of the brainstem CMs were located in the pons (n = 475). The pooled proportions of improved, stable, and worsened functional outcomes after microsurgical resection of brainstem CMs were 56.7% (95% CI 48.4-64.6), 28.6% (95% CI 22.4-35.7), and 12.6% (95% CI 9.6-16.2), respectively. CMs located in the medulla were significantly (p = 0.003) associated with a higher proportion of improved outcome compared with those in the pons and midbrain. Complete resection was achieved in 93.3% (95% CI 89.8-95.7). The immediate postoperative complication rate was 37.2% (95% CI 29.3-45.9), with new-onset cranial nerve deficit being the most common complication. The permanent morbidity rate was 17.3% (95% CI 10.5-27.1), with a low mortality rate of 1% from the compiled study population during a mean follow-up of 58 months. Our analysis indicates that microsurgical resection of brainstem CMs can result in favorable long-term functional outcomes with transient complications in the majority of patients. Complete microsurgical resection of the CM is associated with a lower incidence of CM hemorrhage and the morbidity related to it.


Assuntos
Tronco Encefálico , Microcirurgia , Feminino , Humanos , Adulto , Masculino , Tronco Encefálico/cirurgia , Complicações Pós-Operatórias/epidemiologia , Ponte , Nervos Cranianos
5.
Neurosurg Focus ; 54(5): E9, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37127027

RESUMO

OBJECTIVE: The aim of this study was to describe the efficacy, clinical outcomes, and complications of open cerebrovascular surgery, endovascular surgery, and conservative management of dolichoectatic vertebrobasilar aneurysms (DVBAs). METHODS: Relevant articles were retrieved from PubMed, Scopus, Web of Science, and Cochrane databases according to PRISMA guidelines. A meta-analysis was conducted for clinical presentation, treatment protocols, and clinical outcomes-good (improved or stable clinical status) or poor (deteriorated clinical status or death)-and mortality rates. RESULTS: The 9 identified articles described 41 cases (27.5%) of open cerebrovascular surgery, 61 endovascular procedures (40.9%), and 47 cases (31.5%) of conservative management for DVBAs. The total cohort had a good outcome rate of 51.9% (95% CI 28.3%-74.6%), a poor outcome rate of 45.5% (95% CI 23.0%-70.1%), and a mortality rate of 22.3% (95% CI 11.8%-38.0%). The treatment groups had comparable good clinical outcome rates (open cerebrovascular surgery group: 24.7% [95% CI 2.9%-78.2%]; endovascular surgery group: 69.0% [95% CI 28.7%-92.5%]; conservative management group: 57.7% [95% CI 13.0%-92.5%]; p = 0.19) and poor outcome rates (open vascular surgery group: 75.3% [95% CI 21.8%-97.1%]; endovascular surgery group: 27.2% [95% CI 5.6%-0.70.2%]; conservative management group: 39.9% [95% CI 9.1%-81.6%]; p = 0.15). The treatment groups also had comparable mortality rates (open vascular surgery group: 39.5% [95% CI 11.4%-76.8%]; endovascular surgery group: 15.8% [95% CI 4.4%-43.0%]; conservative management group: 19.2% [95% CI 6.8%-43.5%]; p = 0.23). CONCLUSIONS: The current study of DVBAs illustrated poor outcomes and high mortality rates regardless of the treatment modality. The subgroup analysis showed heterogeneity among the subgroups and advice for personalized management.


Assuntos
Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/métodos
6.
Stroke ; 53(9): 2779-2788, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35770672

RESUMO

BACKGROUND: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT. METHODS: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0-1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0-2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61-3.32]; P<0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14-12.76]; P<0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31-0.96]; P=0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42-2.34]; P=0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16-6.57]; P<0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11-28.92]; P<0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25-0.94]; P=0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31-2.42]; P=0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes. CONCLUSIONS: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.


Assuntos
Arteriopatias Oclusivas , Isquemia Encefálica , Acidente Vascular Cerebral , Angioplastia , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia , Hemorragia Cerebral/etiologia , Humanos , Estudos Retrospectivos , Stents , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Resultado do Tratamento
7.
Neurosurg Focus ; 51(1): E7, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34198247

RESUMO

OBJECTIVE: Acute basilar artery occlusion (BAO) harbors a more guarded prognosis after thrombectomy compared with anterior circulation large-vessel occlusion. Whether this is a function of a greater proportion of atherosclerotic/intrinsic lesions is not well studied. The authors aimed to elucidate the prevalence and predictors of intracranial intrinsic atherosclerotic disease in patients with acute BAO and to compare angiographic and clinical outcomes between patients with BAO secondary to embolic versus intrinsic disease. METHODS: A prospectively maintained stroke database was reviewed for all patients presenting between January 2013 and December 2019 to a tertiary care academic comprehensive stroke center with acute, nontandem BAO. Patient data were extracted, subdivided by stroke mechanism and treatment modality (embolic [thrombectomy only] and intrinsic [thrombectomy + stenting]), and angiographic and clinical results were compared. RESULTS: Of 107 patients, 83 (78%) had embolic occlusions (thrombectomy only) and 24 (22%) had intrinsic disease (thrombectomy + stenting). There was no significant difference in patient age, presenting National Institutes of Health Stroke Scale score, time to presentation, selected medical comorbidities (hypertension, hyperlipidemia, diabetes, and atrial fibrillation), prior stroke, and posterior circulation Alberta Stroke Program Early CT Score. Patients with intrinsic disease were more likely to be active smokers (50% vs 26%, p = 0.04) and more likely to be male (88% vs 48%, p = 0.001). Successful recanalization, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2b or 3, was achieved in 90% of patients and did not differ significantly between the embolic versus intrinsic groups (89% vs 92%, p > 0.99). A 90-day good outcome (modified Rankin Scale [mRS] score 0-2) was found in 37% of patients overall and did not differ significantly between the two groups (36% vs 41%, p = 0.41). Mortality was 40% overall and did not significantly differ between groups (41% vs 36%, p = 0.45). CONCLUSIONS: In the current study, demographic and clinical results for acute BAO showed that compared with intrinsic disease, thromboembolic disease is a more common mechanism of acute BAO, with 78% of patients undergoing thrombectomy alone. However, there was no significant difference in revascularization and outcome results between patients with embolic disease and those with intrinsic disease.


Assuntos
Procedimentos Endovasculares , Acidente Vascular Cerebral , Artéria Basilar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Stents , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombectomia , Resultado do Tratamento
8.
Psychooncology ; 27(5): 1404-1411, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28672093

RESUMO

OBJECTIVE: Adolescents and young adult cancer survivors (AYA) are a unique subpopulation with high levels of distress and unmet need. To date, studies have not disentangled distress due to developmental life stage from distress due to cancer survivorship. This population-based study allowed a direct comparison between AYA cancer survivors, older adult (OA) cancer survivors, and their cancer-free peers. METHODS: We combined 4 annual cycles of the Canadian Community Health Survey (CCHS, 2007-2010) to obtain a final sample of 239 316 respondents. We dichotomized the total sample into AYA (15-39 years, n = 83 770) and OA (40+, n = 155 546). Two standardized questions identified cancer survivors (n = 14 592). The self-reported outcomes of interest included self-perceived health and mental health, and health care professional diagnosed mood and anxiety disorders. We used weighted logistic regression models to examine for associations, including an interaction term to assess for effect modification by age. RESULTS: After adjusting for confounders, cancer survivorship in AYAs was strongly associated with higher prevalence of both mood (OR 2.00, 95% CI 1.44-2.77) and anxiety (OR 2.20, 95% CI 1.70-2.86) disorders as compared to their cancer-free peers. OA survivors had a weaker association in the same direction (OR 1.10, 95% CI 1.01-1.21 and OR 1.15, 95% CI 1.02-1.30, respectively). AYA cancer survivors reported higher levels of poor self-perceived mental health than their cancer-free peers (OR 1.49, 95% CI 1.03-2.14), while there was no significant difference from cancer-free peers for OAs (OR 1.03, 95% CI 0.92-1.15). CONCLUSIONS: AYA cancer survivors experience a significantly higher risk of psychosocial distress than both their cancer-free peers and OA survivors.


Assuntos
Ansiedade/psicologia , Sobreviventes de Câncer/psicologia , Neoplasias/psicologia , Grupo Associado , Qualidade de Vida , Estresse Psicológico/psicologia , Adolescente , Fatores Etários , Idoso , Canadá , Feminino , Humanos , Masculino , Saúde Mental , Neoplasias/mortalidade , Neoplasias/patologia , Prevalência , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
9.
Biochem Soc Trans ; 44(1): 177-84, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26862203

RESUMO

Phosphorylated phosphatidylinositol lipids are crucial for most eukaryotes and have diverse cellular functions. The low-abundance signalling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is critical for cellular homoeostasis and adaptation to stimuli. A large complex of proteins that includes the lipid kinase Fab1-PIKfyve, dynamically regulates the levels of PI(3,5)P2. Deficiencies in PI(3,5)P2 are linked to some human diseases, especially those of the nervous system. Future studies will probably determine new, undiscovered regulatory roles of PI(3,5)P2, as well as uncover mechanistic insights into how PI(3,5)P2 contributes to normal human physiology.


Assuntos
Células/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Animais , Doença , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Fatores de Tempo
10.
Epilepsia ; 57(10): 1697-1708, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27549686

RESUMO

OBJECTIVE: Intracranial monitoring is fundamental to epilepsy surgery, with reported complication rates of 3-17%. We aimed to assess the differences in complication rates between subdural and depth electrodes. METHODS: We conducted a retrospective review of 317 electrode implantation procedures. All documented abnormal postoperative findings were recorded in our study. Those that resulted in a significant alteration of treatment course, including neurologic deficit, long-term medication use, reoperation, or hospital readmission, were deemed clinically significant. When possible, findings were attributed to a particular electrode type based on relative location to each electrode. RESULTS: Postoperative abnormalities were associated with SDE placement in 152 (47.9%) procedures and 40 (25.2%) DE placements (p < 0.001). Twenty-nine (9.1%) clinically significant complications were seen in the subdural electrode (SDE) group compared to 10 associated with DEs (6.3%, p = 0.37). SDEs were associated with increased rates of any postoperative hemorrhage (p < 0.001) or extraaxial collection (p = 0.007). Subdural grid placement was associated with an increased risk of any extraaxial collection (odds ratio [OR 2.42), as well as clinically significant collections (OR 9.47). Previous craniotomy was found to be associated with any abnormal postoperative finding (OR 1.71) as well as radiographic hemorrhage (OR 1.99). Concurrent resection is also associated with abnormal findings (OR 1.83) and extraaxial collections (OR 2.37). The overall complication rate was 9.1%, with 13 procedures (4.1%) resulting in neurologic deficit. However, only two patients (0.6%) had permanent neurologic sequelae resulting from lead placement. SIGNIFICANCE: Subdural electrodes appear to have an increased rate of abnormal postoperative findings, including hemorrhage and extraaxial collections; however, there was no difference in clinically significant findings. Subdural grids also appear to be associated with symptomatic extraaxial collections, and previous craniotomy increases the risk of hemorrhage. Overall, intracranial monitoring remains a safe and effective procedure for localization of operative seizure foci. Patient selection and risk education for various modalities is an essential aspect of preoperative evaluation.


Assuntos
Eletrodos Implantados/efeitos adversos , Epilepsia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/fisiopatologia , Espaço Subdural/cirurgia , Adolescente , Adulto , Idoso , Criança , Eletroencefalografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Tomógrafos Computadorizados , Adulto Jovem
11.
J Biol Chem ; 289(24): 16736-47, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24753258

RESUMO

Cellular energy influences all aspects of cellular function. Although cells can adapt to a gradual reduction in energy, acute energy depletion poses a unique challenge. Because acute depletion hampers the transport of new energy sources into the cell, the cell must use endogenous substrates to replenish energy after acute depletion. In the yeast Saccharomyces cerevisiae, glucose starvation causes an acute depletion of intracellular energy that recovers during continued glucose starvation. However, how the cell replenishes energy during the early phase of glucose starvation is unknown. In this study, we investigated the role of pathways that deliver proteins and lipids to the vacuole during glucose starvation. We report that in response to glucose starvation, plasma membrane proteins are directed to the vacuole through reduced recycling at the endosomes. Furthermore, we found that vacuolar hydrolysis inhibits macroautophagy in a target of rapamycin complex 1-dependent manner. Accordingly, we found that endocytosis and hydrolysis are required for survival in glucose starvation, whereas macroautophagy is dispensable. Together, these results suggest that hydrolysis of components delivered to the vacuole independent of autophagy is the cell survival mechanism used by S. cerevisiae in response to glucose starvation.


Assuntos
Autofagia , Membrana Celular/metabolismo , Endocitose , Glucose/deficiência , Saccharomyces cerevisiae/metabolismo , Vacúolos/metabolismo , Regulação para Baixo , Glucose/metabolismo , Hidrólise , Metabolismo dos Lipídeos , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos Multiproteicos/metabolismo , Transporte Proteico , Proteínas de Saccharomyces cerevisiae/metabolismo , Serina-Treonina Quinases TOR/metabolismo
12.
J Biol Chem ; 289(25): 17812-29, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24790081

RESUMO

Signaling proteins comprised of modular domains have evolved along with multicellularity as a method to facilitate increasing intracellular bandwidth. The effects of intramolecular interactions between modular domains within the context of native proteins have been largely unexplored. Here we examine intra- and intermolecular interactions in the multidomain signaling protein, protein kinase Cα (PKCα). We identify three interactions between two activated PKC molecules that synergistically stabilize a nanomolar affinity homodimer. Disruption of the homodimer results in a loss of PKC-mediated ERK1/2 phosphorylation, whereas disruption of the auto-inhibited state promotes the homodimer and prolongs PKC membrane localization. These observations support a novel regulatory mechanism wherein homodimerization dictates the equilibrium between the auto-inhibited and active states of PKC by sequestering auto-inhibitory interactions. Our findings underscore the physiological importance of context-dependent modular domain interactions in cell signaling.


Assuntos
Membrana Celular/enzimologia , Proteína Quinase C-alfa/metabolismo , Multimerização Proteica/fisiologia , Transdução de Sinais/fisiologia , Animais , Células CHO , Membrana Celular/química , Membrana Celular/genética , Cricetinae , Cricetulus , Humanos , Proteína Quinase 1 Ativada por Mitógeno/química , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/química , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase C-alfa/química , Proteína Quinase C-alfa/genética , Estrutura Terciária de Proteína
13.
World Neurosurg ; 182: 135, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37797682

RESUMO

The differential for vertebrobasilar insufficiency is wide and can be caused by posterior circulation infarcts, steal-type phenomena, or other systemic causes. In the absence of imaging findings explaining symptomology, the utility of appropriate history gathering and dynamic angiography cannot be understated in identifying Bow Hunter's syndrome, a rare cause of dynamic vertebrobasilar insufficiency. We present a case of a 69-year-old man who complained of presyncope and severe dizziness when turning his head towards the right. On examination he had no radiculopathy but did have objective evidence of myelopathy. Computed tomography imaging and dynamic angiography demonstrated C3-C4 right uncovertebral joint hypertrophy and near complete stenosis of the right vertebral artery with dynamic head position towards the right. Given vertebrobasilar insufficiency and myelopathy, he was taken to the operating room for C3-C4 anterior cervical discectomy and fusion with vertebral artery decompression (Video 1). The patient provided consent for the procedure. Standard anterior cervical neck dissection was undertaken with additional platysmal undermining to facilitate exposure of the right uncovertebral joint and transverse processes. The vertebral artery was first decompressed above and below the area of most significant stenosis at the respective transverse foramina before the hypertrophied uncovertebral joint was removed. Next, discectomy and posterior osteophyte removal were completed in typical fashion followed by graft, plate, and screw placement. Postoperatively the patient had immediate resolution of symptoms and continued so at eight month follow-up. Imaging demonstrated return to normal caliber of the right vertebral artery and successful decompression.


Assuntos
Mucopolissacaridose II , Doenças da Medula Espinal , Insuficiência Vertebrobasilar , Masculino , Humanos , Idoso , Mucopolissacaridose II/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/cirurgia , Constrição Patológica/complicações , Angiografia Cerebral/métodos , Descompressão Cirúrgica/métodos , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/etiologia , Insuficiência Vertebrobasilar/cirurgia , Doenças da Medula Espinal/cirurgia
14.
Neurosurg Clin N Am ; 35(3): 355-361, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782528

RESUMO

Developmental venous anomalies (DVAs) are the most common vascular malformation detected on intracranial cross-sectional imaging. They are generally benign lesions thought to drain normal parenchyma. Spontaneous hemorrhages attributed to DVAs are rare and should be ascribed to associated cerebral cavernous malformations, flow-related shunts, or venous outflow obstruction. Contrast-enhanced MRI, susceptibility-weighted imaging, and high-field MRI are ideal tools for visualizing vessel connectivity and associated lesions. DVAs are not generally considered targets for treatment. Preservation of DVAs is an established practice in the microsurgical or radiosurgical treatment of associated lesions.


Assuntos
Veias Cerebrais , Malformações Arteriovenosas Intracranianas , Humanos , Veias Cerebrais/anormalidades , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
15.
World Neurosurg ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823446

RESUMO

OBJECTIVE: Studies assessing aneurysm rupture "risk" based on comparative retrospective analyses of medications taken on presentation may be subject to presentation bias. Are patients with ruptured aneurysms simply less likely to be taking medications than those with unruptured aneurysms? METHODS: A retrospective chart review was conducted among patients with treated aneurysms from June 2016 to July 2023. A step-wise comparison of demographics, clinical characteristics (rupture status), and medications taken upon presentation was performed between ruptured and unruptured cases. RESULTS: One thousand three hundred eleven patients with intracranial aneurysms were included. The majority of patients presenting with ruptured aneurysms took no medications (68%), in contrast to 22% with unruptured aneurysms (P < 0.001). The majority of patients with unruptured aneurysms took 2-5 medications (51%), in contrast to 15% of patients with ruptured aneurysms taking 2-5 medications (P < 0.001). Twelve percent of patients with unruptured aneurysms took more than 5 medications, while only 1% with ruptured aneurysms did (P < 0.001). Thirty-five different medications were associated with unruptured presentation, including all evaluated antiplatelet agents, anti-hypertensives, antacids, pulmonary inhalers, and psychiatric medications (P < 0.05); no medications were associated with rupture on presentation. CONCLUSIONS: One cannot derive conclusions about medications and "risk" of rupture based on analyses at the time of presentation. This study identifies 35 different medications that were statistically significant and associated with an unruptured presentation; it is doubtful that each is "protective" against aneurysm rupture.

16.
World Neurosurg ; 181: e524-e532, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37879435

RESUMO

BACKGROUND: Randomized controlled trials demonstrate that endovascular techniques yield improved outcomes compared with microsurgical approaches. However, not all patients are suitable candidates for endovascular management. This study aimed to determine if healthy patients managed microsurgically could achieve functional outcomes comparable to patients managed endovascularly. METHODS: Patients treated for ruptured aneurysmal subarachnoid hemorrhage at 2 level 1 stroke centers from January 2012 through December 2020 were retrospectively reviewed. All cases were evaluated in an endovascular right of first refusal neurosurgical environment. We collected relevant clinical and follow-up data and created a generalized linear model to identify differences between patients treated endovascularly versus microsurgically. A propensity score model accounting for these differences was used to predict patient outcomes. Functional outcomes were independently assessed using the modified Rankin Scale (mRS) with good functional outcome defined as modified Rankin Scale score <3. RESULTS: The study included 588 patients (211 microsurgical, 377 endovascular); median age was 58 years (interquartile range: 40-86 years); in-hospital mortality was 13%. Age, aneurysm size, and aneurysm location significantly predicted treatment modality (all P < 0.05). After greedy-type matching (210 microsurgical, 210 endovascular), patients managed microsurgically were less likely to be discharged home (odds ratio = 0.6, 95% confidence interval 0.4-0.9, P = 0.01). Functional differences disappeared over time; patients in the 2 treatment arms had similar functional outcomes at 3 months (odds ratio = 1.1, 95% confidence interval 0.7-1.8, P = 0.66) and 1 year after subarachnoid hemorrhage (odds ratio = 1.3, 95% confidence interval 0.8-2.1, P = 0.38). CONCLUSIONS: In an endovascular right of first refusal neurosurgical environment, practitioners can treat patients who are not good endovascular candidates microsurgically and achieve functional outcomes comparable to patients managed endovascularly.


Assuntos
Aneurisma Roto , Procedimentos Endovasculares , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Pessoa de Meia-Idade , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais
17.
J Clin Med ; 13(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38893035

RESUMO

Management of intracranial aneurysms (IAs) is determined by patient age, risk of rupture, and comorbid conditions. While endovascular and microsurgical interventions offer solutions to mitigate the risk of rupture, pharmacological management strategies may complement these approaches or serve as alternatives in appropriate cases. The pathophysiology of IAs allows for the targeting of inflammation to prevent the development and rupture of IAs. The aim of this review is to provide an updated summary of different pharmaceutical management strategies for IAs. Acetylsalicylic acid and renin-angiotensin-aldosterone system (RAAS) inhibitor antihypertensives have some evidence supporting their protective effect. Studies of selective cyclooxygenase-2 (COX-2) inhibitors, statins, ADP inhibitors, and other metabolism-affecting drugs have demonstrated inconclusive findings regarding their association with aneurysm growth or rupture. In this manuscript, we highlight the evidence supporting each drug's effectiveness.

18.
Neurosurgery ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860780

RESUMO

BACKGROUND AND OBJECTIVES: Middle meningeal artery embolization (MMAE) has emerged as a promising modality for chronic/subacute subdural hematoma treatment; however, consensus regarding embolization technique and embolisate has not been achieved. We thus sought to compare the efficacy of distinct MMAE techniques and embolisate. METHODS: An institutional registry was reviewed to identify patients undergoing standalone MMAE for symptomatic chronic/subacute subdural hematoma. Surgical rescue rate and time preceding 50% hematoma resolution were evaluated across 3 technical groups: aggressive penetration (AP), nonaggressive penetration with proximal coil embolization (NP-PC), and nonaggressive penetration alone (NP). Effect sizes were adjusted for demographic, neurological and radiological features through multivariable logistic and Cox regression. RESULTS: Among 117 procedures, 33.3% achieved AP, 36.8% had NP-PC, and 29.9% had NP. The rate of surgical rescue was 2.6% after AP, 9.3% for NP-PC, and 11.4% for NP. In patients not undergoing rescue surgery, 82.4% achieved hematoma resolution ≥50% at a median imaging follow-up of 56 days; AP or NP-PC were each statistically significantly associated with enhanced hematoma resolution as compared with NP (P = .02). Similarly, sensitivity analysis within medium-size hematoma and antiplatelet/anticoagulation-at-admission subgroups revealed a superiority of resolution after AP or NP-PC. A unique, comparative secondary analysis of liquid embolisate (Onyx vs n-butyl cyanoacrylate) revealed no impact on rate of surgical rescue or hematoma resolution. CONCLUSION: AP was associated with the lowest rate of surgical rescue, while both AP and NP-PC were associated with improved rates of hematoma resolution.

19.
World Neurosurg ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735561

RESUMO

BACKGROUND: Traumatic brain injury (TBI) with skull fractures parallel to or crossing venous sinuses is a recognized risk factor for traumatic cerebral venous sinus thrombosis (tCVST). Despite the recognition of this traumatic pathology in the literature, no consensus regarding management has been achieved. This study aimed to evaluate the impact of tCVST on TBI outcomes and related complications. METHODS: Patients within a prospective registry at a level I trauma center from 2014 to 2023 were reviewed to identify tCVST cases. The impact of tCVST presence on Glasgow Outcome Scale scores at 6 months, 30-day mortality, and hospital length of stay were evaluated in multivariable-adjusted analyses. RESULTS: Among 607 patients with TBI, 61 patients were identified with skull fractures extending to the vicinity of venous sinuses with dedicated venography. Twenty-eight of these 61 patients (44.3%) had tCVST. The majority (96.4%) of tCVST were located in a unilateral transverse or sigmoid sinus. Complete recanalization was observed in 28% of patients on follow-up imaging (7/25 with follow-up imaging). None of the 28 patients suffered attributable venous infarcts or thrombus propagation. In the adjusted analysis, there was no difference in the 30-day mortality or Glasgow Outcome Scale at 6 months between patients with and without tCVST. CONCLUSIONS: Unilateral tCVST follows a benign clinical course without associated increased mortality or morbidity. The management of tCVST should be distinct as compared to spontaneous CVST, likely without the need for anticoagulation.

20.
World Neurosurg X ; 22: 100343, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38487683

RESUMO

Objective: Cerebral vasospasm and the resultant delayed cerebral infarction is a significant source of mortality following aneurysmal SAH. Vasospasm is currently detected using invasive or expensive imaging at regular intervals in patients following SAH, thus posing a risk of complications following the procedure and financial burden on these patients. Currently, there is no blood-based test to detect vasospasm. Methods: PubMed, Web of Science, and Embase databases were systematically searched to retrieve studies related to cerebral vasospasm, aneurysm rupture, and biomarkers. The study search dated from 1997 to 2022. Data from eligible studies was extracted and then summarized. Results: Out of the 632 citations screened, only 217 abstracts were selected for further review. Out of those, only 59 full text articles met eligibility and another 13 were excluded. Conclusions: We summarize the current literature on the mechanism of cerebral vasospasm and delayed cerebral ischemia, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future bloodbased test to detect vasospasm. Efforts should be focused on clinical-translational approaches to create such a test to improve treatment timing and prediction of vasospasm to reduce the incidence of delayed cerebral infarction.

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