Cerebral vasospasm following subarachnoid hemorrhage has high morbidity and mortality. Mathematical modeling of the progression of the condition provides insight to improve clinical treatment of patients post subarachnoid hemorrhage. An existing model of the clotting cascade is expanded to include the theoretical conditions of cerebral vasospasm. We consider clotting factor XIIIa, which has been implicated as a primary cause of the entrenchment of the smaller diameter. Solutions for clotting are used as boundary conditions to solve the concentration of diffusible clotting factors in the vessel wall and cerebrospinal fluid (CSF). Each domain (clot, vessel wall, CSF) is described by a separate initial-boundary value problem, requiring unique conditions, reaction-diffusion equations, and diffusion coefficients. Additionally, the results from the first domain (the clot) provide a subset of the boundary conditions for the second and third domains (arterial wall and CSF, respectively). Although this approach captures many detailed components of the clotting process, a simpler method for investigating the formation and dissolution of a clot post subarachnoid hemorrhage is to neglect the bulk of the clot cascade to focus on the most salient features, namely, the formation of cross-linked fibrin and the degradation of fibrin by plasmin. By assuming first order kinetics in the initial hours following hemorrhage, we find a simplified expression with kinetic rates that may be adjusted depending on experimental conditions.

No description available.

Subarachnoid hemorrhage (SAH) is a disease with high risk of mortality and morbidity. Elderly patients have an even higher risk of poor outcome. The incidence of SAH increases with age and the elderly constitute a substantial and increasing proportion of the population. Thus, the management of elderly SAH patients is an imminent clinical challenge. Time trends in clinical management and outcome were investigated in 281 SAH patients aged ≥65 years admitted over an 18-year period. The volume of elderly patients, especially patients ≥70 years and patients in worse clinical condition increased over time. The proportion of patients with favorable outcome increased over time, without an increase in severely disabled patients. Technical results and clinical outcome of endovascular aneurysm treatment (EVT) was investigated in 62 elderly SAH patients. EVT can be performed in elderly SAH patients with high technical success, acceptable aneurysm occlusion degree, acceptable procedural complication rate, and fair outcome results. EVT was compared to neurosurgical clipping (NST) in 278 elderly SAH patients in the International Subarachnoid Aneurysm Trial. In good grade elderly SAH patients, EVT should probably be the favored treatment for internal carotid and posterior communicating artery aneurysms, while elderly patients with middle cerebral artery aneurysms appear to benefit from NST. Occurrence of secondary insults and their impact on clinical deterioration were studied in 99 patients with severe SAH. High intracranial pressure increased and high cerebral perfusion pressure decreased the risk of clinical deterioration. Elderly patients had less intracranial hypertension insults and more hypertensive, hypotensive and hypoxemic insults. Good outcome was achieved in 24% of elderly patients with severe SAH, and the proportion of severe disability was similar to that of younger patients. Patient age was not a significant predictor for vasospasm in 413 SAH patients when admission and treatment variables were adjusted for with multiple logistic regression.

Background: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) has been extensively investigated, but the impact of collateralization remains unclear. We investigated the predictive value of collateral activation for delayed cerebral ischemia (DCI)-related infarctions and functional outcome. Methods: Data from 43 patients with CVS (January 2014 to August 2021) were evaluated for the angiographic presence of leptomeningeal and ophthalmic collaterals (anterior falcine artery (AFA), supratrochlear artery (STA), dorsal nasal artery (DNA)) on internal carotid artery angiograms. Vasospasm-related infarction and the modified Rankin Scale (mRS) score after six months were chosen as the endpoints. Results: 77% of the patients suffered from DCI-related infarctions. In 233 angiograms (at hospitalization, before spasmolysis, after six months), positive vessel signs were observed in 31 patients for STA, 35 for DNA, and 31 for AFA. The STA sign had the highest positive (84.6%) and negative (85.7%) predictive value for unfavorable outcome (mRS 4–6) in patients aged 50 years. DNA and AFA signs were not meaningful predictors for either endpoint. Leptomeningeal collaterals showed a positive Pearson’s correlation with the STA sign in 87.5% (p = 0.038) without providing any prediction for either endpoint. Conclusions: The STA sign is associated with clinical outcome in patients with CVS after SAH aged 50 years, and was correlated with the occurrence of leptomeningeal collaterals.

Background: Cerebral vasospasm (CVS) continues to account for high morbidity and mortality in patients surviving the initial aneurysmal subarachnoid hemorrhage (SAH). Nimodipine is the only drug known to reduce delayed cerebral ischemia (DCI), but it is believed not to affect large vessel CVS. Milrinone has emerged as a promising option. Our retrospective study focused on the effectiveness of the intra-arterial application of both drugs in monotherapy and combined therapy. Methods: We searched for patients with aneurysmal SAH, angiographically confirmed CVS, and at least one intra-arterial pharmacological angioplasty. Ten defined vessel sections on angiograms were assessed before and after vasodilator infusion. The improvement in vessel diameters was compared to the frequency of DCI-related cerebral infarction before hospital discharge and functional outcome reported as the modified Rankin Scale (mRS) score after 6 months. Results: Between 2014 and 2021, 132 intra-arterial interventions (144 vascular territories, 12 bilaterally) in 30 patients were analyzed for this study. The vasodilating effect of nimodipine was superior to milrinone in all intradural segments. There was no significant intergroup difference concerning outcome in mRS (p = 0.217). Only nimodipine or the combined approach could prevent DCI-related infarction (both 57.1%), not milrinone alone (87.5%). Both drugs induced a doubled vasopressor demand due to blood pressure decrease, but milrinone alone induced tachycardia. Conclusions: The monotherapy with intra-arterial nimodipine was superior to milrinone. Nimodipine and milrinone may be used complementary in an escalation scheme with the administration of nimodipine first, complemented by milrinone in cases of severe CVS. Milrinone monotherapy is not recommended.

Hemorragia subaracnoidea aneurismática (HSAa) é considerada causa importante de morte e de sequelas neurológicas. A taxa de mortalidade desta doença pode alcançar 50% nos primeiros dois meses após sangramento de aneurisma encefálico. Apesar dos avanços científicos da modernidade, o resultado do tratamento da HSAa não mudou nos últimos anos. O presente estudo avaliou o papel de 14 biomarcadores genéticos, incluindo o polimorfismo (SNP) do gene eNOS, em pacientes da Amazônia com HSAa, para verificar as alterações alélicas associadas ao risco de vasoespasmo encefálico e déficit neurológico tardio. Avaliou-se a ancestralidade desta amostra de pacientes em que se utilizou 48 marcadores para identificar possível etnia associada à predisposição ao VE. Investigou-se 14 biomarcadores genéticos no tocante à resposta inflamatória encefálica na HSAa. Foram avaliados 265 doentes que foram divididos em dois grupos: grupo I (pacientes com vasoespasmo encefálico) e grupo 2 (pacientes sem vasoespasmo). A média das idades foi 51 anos, havia 224 mulheres (84%) e 124 pacientes (46,79%) apresentaram vasoespasmo encefálico (VE). A maior incidência de VE ocorreu na idade entre 50 e 59 anos. Tabagismo e hipertensão arterial sistêmica foram os fatores de risco mais associados à VE. Aneurismas encefálicos de tamanho pequeno e médio predominaram nesta casuística. As escalas amarela e vermelha do VASOGRADE associaram-se ao risco de VE (p < 0,001). Não houve variação na distribuição ancestral entre os grupos estudados e o que ocorre na população brasileira saudável na região Amazônica. O gene da eNOS com seus respectivos polimorfismos T-786C e 27VNTR4 correlacionaram-se com VE. Outros marcadores observados foram TP53, CASP8, ACE2, IL4 e XRCC1. O gene TP53 (modelo recessivo alelo 1) mostrou-se ser um fator protetor de VE, enquanto que genes com mutações INDEL CASP8 (modelo recessivo alelo 2) e o XRCC1 (modelo recessivo alelo 1) mostraram tendência ao desenvolvimento de VE com risco 2 vezes maior e 1,4 vezes maior que o grupo II (p < 0,001). Conclui-se que SNPs da eNOS se correlacionam com desenvolvimento de VE sintomático pós-HSAa. Este estudo também mostrou o papel dos marcadores inflamatórios na HSAa, o que auxiliaria na condução da terapia clínica. / Aneurysmal subarachnoid hemorrhage (aSAH) is a leading cause of premature death and neurological disability. It is considered as a devastating condition that accounts to 50% of mortality during the first two months after a hemorrhagic event. Despite foremost advances in the clinical management of post-aSAH patients, the rates of mortality and morbidity have not changed in recent years. This study appraised the role of 14 genetic biomarkers, including the eNOS polymorphism (SNP) between Amazon\'s patients with aSAH, as means to document how variant alleles are related to a higher disposition to cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). 265 patients were evaluated and then divided into two clusters: Group I (with symptomatic CV) and group II (presenting no symptomatic CV). The median ages of patients were 51.61 years of age, 224 (84.52%) were women and 124 patients (46.97%) had symptoms of cerebral vasospasm (CV). Tobacco smoking and systemic arterial hypertension are the risk factors most associated to CV. In the course of this research, most aneurysms found were small and medium-sized. The score VASOGRADE yellow and VASOGRADE red presented a high risk of CV (p < 0.001). We established a panel of 48 ancestry informative markers for estimating which ethnicity could present a predisposition to CV. There was no variation in the ancestral distribution between study groups and healthy brazilian folk over the Amazon region. The eNOS gene with its polymorphisms T-786C and 27 VNTR4 were correlated to CV. Other markers were accomplished: TP53, CASP8, ACE2, IL4, and XRCC1. The TP53 gene (recessive genetic model allele 1) supporting evidence of the protective role to CV. Whilst other genes with INDEL mutation like as CASP8 (recessive model allele 2) and the XRCC1 (recessive model allele 1) indicated a propensity to spread out CV with odds 2-fold higher, and 1.414 times greater than group II (p < 0.001). It follows that eNOS SNPs correlate to a positive association with a syntomatic CV post-aSAH. Also, this study showed up the role of inflammatory markers at aSAH to a further educated therapeutic choice for a better clinical response

Hemorragia subaracnoidea aneurismática (HSAa) é considerada causa importante de morte e de sequelas neurológicas. A taxa de mortalidade desta doença pode alcançar 50% nos primeiros dois meses após sangramento de aneurisma encefálico. Apesar dos avanços científicos da modernidade, o resultado do tratamento da HSAa não mudou nos últimos anos. O presente estudo avaliou o papel de 14 biomarcadores genéticos, incluindo o polimorfismo (SNP) do gene eNOS, em pacientes da Amazônia com HSAa, para verificar as alterações alélicas associadas ao risco de vasoespasmo encefálico e déficit neurológico tardio. Avaliou-se a ancestralidade desta amostra de pacientes em que se utilizou 48 marcadores para identificar possível etnia associada à predisposição ao VE. Investigou-se 14 biomarcadores genéticos no tocante à resposta inflamatória encefálica na HSAa. Foram avaliados 265 doentes que foram divididos em dois grupos: grupo I (pacientes com vasoespasmo encefálico) e grupo 2 (pacientes sem vasoespasmo). A média das idades foi 51 anos, havia 224 mulheres (84%) e 124 pacientes (46,79%) apresentaram vasoespasmo encefálico (VE). A maior incidência de VE ocorreu na idade entre 50 e 59 anos. Tabagismo e hipertensão arterial sistêmica foram os fatores de risco mais associados à VE. Aneurismas encefálicos de tamanho pequeno e médio predominaram nesta casuística. As escalas amarela e vermelha do VASOGRADE associaram-se ao risco de VE (p < 0,001). Não houve variação na distribuição ancestral entre os grupos estudados e o que ocorre na população brasileira saudável na região Amazônica. O gene da eNOS com seus respectivos polimorfismos T-786C e 27VNTR4 correlacionaram-se com VE. Outros marcadores observados foram TP53, CASP8, ACE2, IL4 e XRCC1. O gene TP53 (modelo recessivo alelo 1) mostrou-se ser um fator protetor de VE, enquanto que genes com mutações INDEL CASP8 (modelo recessivo alelo 2) e o XRCC1 (modelo recessivo alelo 1) mostraram tendência ao desenvolvimento de VE com risco 2 vezes maior e 1,4 vezes maior que o grupo II (p < 0,001). Conclui-se que SNPs da eNOS se correlacionam com desenvolvimento de VE sintomático pós-HSAa. Este estudo também mostrou o papel dos marcadores inflamatórios na HSAa, o que auxiliaria na condução da terapia clínica. / Aneurysmal subarachnoid hemorrhage (aSAH) is a leading cause of premature death and neurological disability. It is considered as a devastating condition that accounts to 50% of mortality during the first two months after a hemorrhagic event. Despite foremost advances in the clinical management of post-aSAH patients, the rates of mortality and morbidity have not changed in recent years. This study appraised the role of 14 genetic biomarkers, including the eNOS polymorphism (SNP) between Amazon\'s patients with aSAH, as means to document how variant alleles are related to a higher disposition to cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). 265 patients were evaluated and then divided into two clusters: Group I (with symptomatic CV) and group II (presenting no symptomatic CV). The median ages of patients were 51.61 years of age, 224 (84.52%) were women and 124 patients (46.97%) had symptoms of cerebral vasospasm (CV). Tobacco smoking and systemic arterial hypertension are the risk factors most associated to CV. In the course of this research, most aneurysms found were small and medium-sized. The score VASOGRADE yellow and VASOGRADE red presented a high risk of CV (p < 0.001). We established a panel of 48 ancestry informative markers for estimating which ethnicity could present a predisposition to CV. There was no variation in the ancestral distribution between study groups and healthy brazilian folk over the Amazon region. The eNOS gene with its polymorphisms T-786C and 27 VNTR4 were correlated to CV. Other markers were accomplished: TP53, CASP8, ACE2, IL4, and XRCC1. The TP53 gene (recessive genetic model allele 1) supporting evidence of the protective role to CV. Whilst other genes with INDEL mutation like as CASP8 (recessive model allele 2) and the XRCC1 (recessive model allele 1) indicated a propensity to spread out CV with odds 2-fold higher, and 1.414 times greater than group II (p < 0.001). It follows that eNOS SNPs correlate to a positive association with a syntomatic CV post-aSAH. Also, this study showed up the role of inflammatory markers at aSAH to a further educated therapeutic choice for a better clinical response

No description available.