Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study / Homocisteína sérica em pacientes com aneurismas rotos e não rotos: um estudo caso-controle

Abstract Background There is very few data regarding homocysteine's influence on the formation and rupture of intracranial aneurysms. Objective To compare homocysteine levels between patients with ruptured and unruptured intracranial aneurysms, and to evaluate possible influences of this molecule on vasospasm and functional outcomes. Methods This is a retrospective, case-control study. We evaluated homocysteinemia differences between patients with ruptured and unruptured aneurysms; and the association of homocysteine levels with vasospasm and functional outcomes. Logistic regressions were performed. Results A total of 348 participants were included: 114 (32.8%) with previous aneurysm rupture and 234 (67.2%) with unruptured aneurysms. Median homocysteine was 10.75μmol/L (IQR = 4.59) in patients with ruptured aneurysms and 11.5μmol/L (IQR = 5.84) in patients with unruptured aneurysms. No significant association was detected between homocysteine levels and rupture status (OR = 0.99, 95% CI = 0.96-1.04). Neither mild (>15μmol/L; OR = 1.25, 95% CI 0.32-4.12) nor moderate (>30μmol/L; OR = 1.0, 95% CI = 0.54-1.81) hyperhomocysteinemia demonstrated significant correlations with ruptured aneurysms. Neither univariate (OR = 0.86; 95% CI 0.71-1.0) nor multivariable age-adjusted (OR = 0.91; 95% CI = 0.75-1.05) models evidenced an association between homocysteine levels and vasospasm. Homocysteinemia did not influence excellent functional outcomes at 6 months (mRS≤1) (OR = 1.04; 95% CI = 0.94-1.16). Conclusion There were no differences regarding homocysteinemia between patients with ruptured and unruptured intracranial aneurysms. In patients with ruptured aneurysms, homocysteinemia was not associated with vasospasm or functional outcomes.

RESUMO Antecedentes Existem poucos dados sobre a influência da homocisteína na formação e rotura de aneurismas intracranianos (AI). Objetivo Comparar os níveis de homocisteína entre pacientes com AI rotos e não rotos e influências no vasoespasmo e resultados funcionais. Métodos Estudo caso-controle, que avaliou as diferenças de homocisteinemia entre pacientes com aneurismas rotos e não rotos, além da associação entre níveis de homocisteína, vasoespasmo e estado funcional. Regressões logísticas foram realizadas. Resultados Um total de 348 participantes foram incluídos: 114 (32,8%) com aneurismas rotos e 234 (67,2%) não rotos. A homocisteína mediana foi de 10,75μmol/L (IQR = 4,59) nos rotos e 11,5μmol/L (IQR = 5,84) nos não rotos. Não houve associação significativa entre os níveis de homocisteína e o status de ruptura (OR = 0,99, 95% CI = 0,96-1,04). Nem a hiperhomocisteinemia leve (>15μmol/L; OR = 1,25, 95% CI = 0,32-4,12) nem a moderada (>30μmol/L; OR = 1,0, 95% CI = 0,54-1,81) mostraram correlações significativas com aneurismas rotos. Modelos univariados (OR = 0,86; 95% CI = 0,71-1,0) e multivariados ajustados por idade (OR = 0,91; 95% CI = 0,75-1,05) não evidenciaram associação entre homocisteína e vasoespasmo. A homocisteinemia não influenciou resultados funcionais excelentes em seis meses (mRS ≤ 1) (OR = 1,04; 95% CI = 0,94-1,16). Conclusão Não houve diferenças em relação à homocisteinemia entre pacientes com aneurismas intracranianos rotos e não rotos. Em pacientes com aneurismas rotos, a homocisteinemia não foi associada ao vasoespasmo ou resultados funcionais.

Complicaciones del tratamiento endovascular y quirúrgico en las hemorragias subaracnoideas aneurismáticas en Uruguay: análisis prospectivo de una serie de 211 casos

Introducción: si bien varios estudios han abordado la comparación entre el tratamiento endovascular y el clipado quirúrgico de aneurismas rotos, no existe aún evidencia firme respecto a la utilización de una u otra técnica en términos de seguridad y mejor pronóstico. El objetivo de este trabajo es analizar las distintas modalidades de tratamiento de la hemorragia subaracnoidea (HSA) implementadas en Uruguay y su impacto sobre la curación del aneurisma y el pronóstico de los pacientes. Material y método: estudio prospectivo y multicéntrico que incluyó a todos los pacientes mayores de 18 años que fueron asistidos por HSA espontánea aneurismática en Uruguay entre el 1 de noviembre de 2019 y el 31 de octubre de 2020. Fueron relevadas las características clínico-epidemiológicas y comorbilidades al momento del diagnóstico, el tipo de tratamiento recibido y variables de evolución clínica durante los siguientes seis meses. Los datos fueron procesados a través del software estadístico Statistical Package for Social Sciences (SPSS) y el nivel de significación utilizado en los test fue de 5%. Debido al carácter multicéntrico y nacional del estudio, debió ser sometido a evaluación por todos los comités de ética de las instituciones de salud participantes. Resultados: se observó un total de 211 casos en el período evaluado. La media de edad fue de 57 años con predominancia del sexo femenino (75%). En el 74% de los casos fue indicado algún tipo de tratamiento específico (43% cirugía abierta y 31% terapia endovascular), mientras al resto de los pacientes no se les pudo tratar el aneurisma por su grave situación neurológica; 52 pacientes tuvieron complicaciones vinculadas al tratamiento recibido, observándose una mayor proporción de estas en el caso de la cirugía abierta respecto a la terapia endovascular (42% vs 21,5%; p=0,008). Conclusiones: se observó una mayor tasa de complicaciones en el tratamiento quirúrgico, sin impacto en la morbimortalidad. De los factores predictores independientes de mala evolución clínica encontrados, el único vinculado al tipo de tratamiento fue la presencia de isquemia extensa.

Introduction: While several studies have addressed the comparison between endovascular treatment and surgical clipping of ruptured aneurysms, there is still no definitive evidence regarding the use of one or the other in terms of safety and improved prognosis. The objective of this study is to analyze the various modalities of subarachnoid hemorrhage (SAH) treatment implemented in Uruguay and their impact on aneurysm resolution and patient prognosis. Method: This is a prospective, multicenter study that includes all patients over 18 years of age who were treated for spontaneous aneurysmal subarachnoid hemorrhage in Uruguay between November 1, 2019, and October 31, 2020. We collected and examined clinical-epidemiological characteristics and comorbidities at the time of diagnosis, the type of treatment received, and clinical outcome variables over the following 6 months. The data were analysed using the Statistical Package for Social Sciences (SPSS) software, and a significance level of 5% was applied in the tests. Due to the multicenter and national nature of the study, it had to be submitted for evaluation to all the Ethics Committees of the participating healthcare institutions. Results: A total of 211 cases were observed during the evaluated period. The mean age was 57 years with a predominance of females (75%). In 74% of the cases, some form of specific treatment was recommended (43% open surgery and 31% endovascular therapy), while the remaining patients could not undergo aneurysm treatment due to their severe neurological condition. 52 patients experienced complications related to the treatment received, with a higher proportion of these in the case of open surgery compared to endovascular therapy (42% vs. 21,5%; p=0,008). Conclusions: A higher rate of complications was observed in the surgical treatment, with no impact on morbidity and mortality. Among the independent predictors of poor clinical outcomes identified, the only one related to the type of treatment was the presence of extensive ischemia.

As campanhas de prevenção e promoção da saúde, bem como os avanços na medidas terapêuticas voltadas para pacientes neurocríticos conseguiram reduzir a incidência de pacientes com lesão cerebral aguda que evoluem para morte encefálica (ME). No entanto, na maioria dos países latino-americanos, os órgãos que podem ser perfundidos adequados para transplante (TX) vêm de doadores falecidos em ME. A doação em assistolia e em particular a doação em assistolia controlada (DAC), é uma opção aceita e válida para a obtenção de órgãos, o que contribuiria para a redução das listas de espera para transplantes. Durante o processo DAC, são aplicados conceitos com forte cunho bioético, que são fundamentais na o momento da tomada de decisão. Este artigo tem como objetivo analisar esses conceitos, com o objetivo de oferecer ferramentas válidas à equipe de saúde, para os processos em que há deliberação moral como ocorre na doação de órgãos em assistolia controlada considerada parte integrante dos cuidados de fim de vida.

Correlation between tomographic scales and vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage / Correlación entre escalas tomográficas y vasoespasmo e isquemia cerebral diferida en la hemorragia subaracnoidea aneurismática

ABSTRACT Objective: To determine the prevalence of sonographic vasospasm and delayed ischemic deficit in patients with aneurysmal subarachnoid hemorrhage, to evaluate the correlation between different tomographic scales and these complications, and to study prognostic factors in this group of patients. Methods: This was a prospective study of patients admitted to the intensive care unit with a diagnosis of aneurysmal subarachnoid hemorrhage. The prevalence of sonographic vasospasm and radiological delayed cerebral ischemia was analyzed, as was the correlation between different tomographic scales and these complications. Results: A total of 57 patients were studied. Sixty percent of the patients developed sonographic vasospasm, which was significantly associated with delayed cerebral ischemia and mortality. The Claassen and Hijdra scales were better correlated with the development of cerebral vasospasm (areas under the curve of 0.78 and 0.68) than was Fisher's scale (0.62). Thirty-two patients (56.1%) developed cerebral infarction on CT; the significantly associated factors were poor clinical grade at admission (p = 0.04), sonographic vasospasm (p = 0.008) and severity of vasospasm (p = 0.015). Only the semiquantitative Hijdra scale was significantly correlated with the development of radiological delayed cerebral ischemia (p = 0.009). The patients who presented cerebral infarction had worse neurological evolution and higher mortality. Conclusion: This is the first study in our environment on the subject. The Claassen and Hijdra tomographic scales showed better prognostic performance than the Fisher scale for the development of cerebral vasospasm. The finding of sonographic vasospasm could be a noninvasive criterion for the early detection of delayed cerebral ischemia and neurological deterioration in patients with aneurysmal subarachnoid hemorrhage.

RESUMO Objetivo: Determinar la prevalencia de vasoespasmo sonográfico y déficit isquémico diferido en pacientes con hemorragia subaracnoidea aneurismática, evaluar la correlación entre las diferentes escalas tomográficas con dichas complicaciones, así como estudiar los factores pronósticos en este grupo de pacientes. Métodos: Estudio prospectivo de pacientes ingresados a la unidad de cuidados intensivos con diagnóstico de hemorragia subaracnoidea aneurismática. Se analizó la prevalencia de vasoespasmo sonográfico e isquemia cerebral diferida radiológica, así como la correlación entre diferentes escalas tomográficas con dichas complicaciones. Resultados: Se estudiaron 57 pacientes. El 60% de los pacientes desarrollaron vasoespasmo sonográfico, el cual se asoció significativamente con isquemia cerebral diferida y mortalidad. Las escalas de Claassen y de Hijdra tuvieron una mejor correlación con el desarrollo de vasoespasmo cerebral (área bajo la curva de 0,78 y 0,68) que la de Fisher (0,62). Treinta y dos pacientes (56,1%) desarrollaron infarto cerebral en la TC, siendo los factores que se asociaron en forma estadísticamente significativa al mismo: pobre grado clínico al ingreso (p = 0,04), vasoespasmo sonográfico (p = 0,008) y severidad del vasoespasmo (p = 0,015). Solamente la escala semicuantitativa de Hijdra se correlacionó significativamente con el desarrollo de isquemia cerebral diferida radiológica (p = 0,009). Los pacientes que presentaron infarto cerebral tuvieron peor evolución neurológica y mayor mortalidad. Conclusion: Se presenta el primer estudio en nuestro medio sobre el tema. Las escalas tomográficas de Claassen y Hijdra presentaron un mejor rendimiento pronóstico que la de Fisher para desarrollo de vasoespasmo cerebral. El hallazgo de vasoespasmo sonográfico podría ser un criterio no invasivo de detección temprana de isquemia cerebral diferida y peoría neurológica en los pacientes con hemorragia subaracnoidea aneurismática.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and prognosis after aneurysmal subarachnoid hemorrhage: a cohort study / Razão neutrófilos-linfócitos e razão plaquetas-linfócitos e o prognóstico de hemorragia subaracnóidea aneurismática: um estudo de coorte

Abstract Background Subarachnoid hemorrhage (SAH) prognosis remains poor. Vasospasm mechanism might be associated with inflammation. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as inflammation markers and prognostic predictors. Objective We aimed to investigate NLR and PLR in admission as predictors of angiographic vasospasm and functional outcome at 6 months. Methods This cohort study included consecutive aneurysmal SAH patients admitted to a tertiary center. Complete blood count was recorded at admission before treatment. White blood cell count, neutrophil count, lymphocyte count, platelet count, NLR, and PLR were collected as independent variables. Vasospasm occurrence-modified Rankin scale (mRS), Glasgow outcome scale (GOS), and Hunt-Hess score at admission and at 6 months were recorded as dependent variables. Multivariable logistic regression models were used to adjust for potential confounding and to assess the independent prognostic value of NLR and PLR at admission. Results A total of 74.1% of the patients were female, with mean age of 55.6 ± 12.4 years. At admission, the median Hunt-Hess score was 2 (interquartile range [IQR] 1), and the median mFisher was 3 (IQR 1). Microsurgical clipping was the treatment for 66.2% of the patients. Angiographic vasospasm incidence was 16.5%. At 6 months, the median GOS was 4 (IQR 0.75), and the median mRS was 3 (IQR 1.5). Twenty-one patients (15.1%) died. Neutrophil-to-lymphocyte ratio and PLR levels did not differ between favorable and unfavorable (mRS > 2 or GOS < 4) functional outcomes. No variables were significantly associated with angiographic vasospasm. Conclusion Admission NLR and PLR presented no value for prediction of functional outcome or angiographic vasospasm risk. Further research is needed in this field.

Resumo Antecedentes O prognóstico da hemorragia subaracnoidea (HSA) permanece ruim. Vasoespasmo pode estar associado à inflamação. Razões neutrófilo-linfócito (NLR) e plaqueta-linfócito (PLR) têm sido estudadas como marcadores de inflamação e prognóstico. Objetivo Investigar NLR e PLR na admissão como preditores de vasoespasmo angiográfico e desfecho aos 6 meses. Métodos Este estudo de coorte incluiu pacientes consecutivos com HSA aneurismática de um centro terciário. Contagem de leucócitos, neutrófilos, linfócitos e plaquetas, proporção de neutrófilos para linfócitos e de plaquetas para linfócitos foram coletados como variáveis independentes. Ocorrência de vasoespasmo, escala de Rankin modificada, escala de desfecho de Glasgow e o escore de Hunt-Hess na admissão e 6 meses após a mesma foram registradas como variáveis dependentes. Modelos de regressão logística multivariável foram usados para ajustar potenciais fatores de confusão e avaliar valor prognóstico independente de NLR e PLR. Resultados Um total de 74,1% pacientes eram do sexo feminino, com idade média de 55,6 ± 12,4 anos. Na admissão, a pontuação média de Hunt-Hess foi de 2 (IQR 1) e a mediana de mFisher foi de 3 (IQR 1). Clipagem microcirúrgica foi o tratamento escolhido para 66,2% dos pacientes. A incidência de vasoespasmo angiográfico foi de 16,5%. Aos 6 meses, a escala de desfecho de Glasgow mediana era 4 (IQR 0,75) e a escala de Rankin modificada mediana era 3 (IQR 1,5). Vinte e um pacientes (15,1%) morreram. Os níveis de NLR e PLR não diferiram entre resultados funcionais favoráveis e desfavoráveis (mRS > 2 ou GOS < 4). Nenhuma variável foi significativamente associada ao vasoespasmo angiográfico. Conclusão Razão neutrófilo-linfócito e a PLR não apresentaram valor preditivo de desfecho funcional ou risco de vasoespasmo angiográfico. Mais pesquisas são necessárias neste campo.

Comportamiento de indicadores relacionados con la asistencia a pacientes con hemorragia subaracnoidea espontánea en la provincia de Cienfuegos

Fundamento: la importancia sanitaria de la hemorragia subaracnoidea espontánea, como problema de salud, es un hecho reconocido. Objetivo determinar el comportamiento de algunos indicadores relacionados con la asistencia médica a pacientes con hemorragia subaracnoidea espontánea, en el contexto provincial. Métodos estudio observacional, descriptivo-correlacional y retrospectivo, de 96 pacientes con hemorragia subaracnoidea espontánea entre 2016 y 2021. Se analizó el comportamiento de indicadores seleccionados, en su relación con diversas variables. En el análisis estadístico se utilizó como estadígrafo el Odds Ratio y su intervalo de confianza. Resultados el 22 % de los pacientes fue diagnosticado pasadas las primeras 48 horas del inicio de los síntomas, mientras que 13 enfermos (14 %) requirieron más de una asistencia para el diagnóstico. La ocurrencia de diagnóstico tardío cuando no se identificó el sangramiento en la primera consulta fue significativa (OR 21,8[5,1;91,8]). Doce pacientes fueron admitidos fuera de unidades especializadas; esta situación se observó más en pacientes menores de 60 años (21% vs 4 %; OR 5,7[1,1;27,9]), y en quienes el diagnóstico se realizó después de las 48 horas del inicio de las manifestaciones (29 % vs 8 %; OR 4,6[1,3;16,2]). De los 35 pacientes trasladados a otra institución para tratamiento neuroquirúrgico solo cuatro (12 %) fueron evacuados en las primeras 72 horas. Conclusiones se identifican brechas en la atención al paciente con hemorragia subaracnoidea en el contexto provincial; se destacan el ingreso de enfermos fuera de unidades especializadas y el traslado tardío a instituciones con servicio de cirugía neurovascular.

Background: the spontaneous subarachnoid hemorrhage's health importance, it's recognized as a health problem. Objective: to determine the behavior of some indicators related to medical care for patients with spontaneous subarachnoid hemorrhage, in the provincial context. Methods: Observational, descriptive-correlational and retrospective study of 96 patients with spontaneous subarachnoid hemorrhage between 2016 and 2021. The behavior of selected indicators was analyzed in relation to various variables. In the statistical analysis, the Odds Ratio and its confidence interval were used as statisticians. Results: 22% of the patients were diagnosed after the first 48 hours after the onset of symptoms, while 13 patients (14%) required more than one assistance for diagnosis. The occurrence of late diagnosis when bleeding was not identified at the first visit was significant (OR 21.8[5.1;91.8]). Twelve patients were admitted outside of specialized units; this situation was observed more in patients under 60 years of age (21% vs 4%; OR 5.7[1.1;27.9]), and in whom the diagnosis was made 48 hours after the onset of manifestations (29% vs 8%; OR 4.6[1.3;16.2]). Of the 35 patients transferred to another institution for neurosurgical treatment, only four (12%) were evacuated in the first 72 hours. Conclusions: gaps are identified in the patients' care with subarachnoid hemorrhage in the provincial context; The admission of patients outside specialized units and the late transfer to institutions with neurovascular surgery service stand out.

Embolización de aneurismas intracraneales múltiples en sesión única

Objetivo: Determinar los resultados clínicos y angiográficos en pacientes con aneurismas intracraneales múltiples tratados endovascularmente en una única sesión. Materiales y Métodos: Se incluyó a todos los pacientes mayores de 18 años con aneurismas múltiples (≥2), rotos o no rotos, tratados con terapia endovascular en una única sesión entre 2019 y 2021. Se recolectaron los datos clínicos y angiográficos. Se determinó la tasa de oclusión inmediata y del seguimiento. La escala de Rankin modificado se usó para valorar el resultado clínico. Resultados: Se trataron 25 pacientes, de los cuales 14 se presentaron con hemorragia subaracnoidea. Se diagnosticaron un total de 78 aneurismas, de los cuales 59 aneurismas fueron tratados. La localización más frecuente fue el segmento oftálmico. La altura máxima promedio fue de 5.2mm, lo cual tuvo diferencia estadística significativa con el estado de ruptura (p ≤ 0.02). El principal tipo de tratamiento endovascular fue la técnica de remodeling en el 39 % de casos. El Raymond Roy inmediato fue I en el 60 % y IIIa en el 35 % de casos. La tasa de complicaciones fue del 24 % y de mortalidad fue del 8 %. Conclusiones: El tratamiento endovascular en una única sesión es una opción efectiva y segura en casos de aneurismas intracraneales múltiples en nuestra institución con tasa de oclusión y complicaciones aceptable.

Objective: To determine clinical and angiographical outcomes in patients with multiple intracranial aneurysms who underwent endovascular therapy in a single session. Materials and Methods: Patients older than 18 years with multiple (≥2) ruptured or non-ruptured aneurysms were included, and all of them underwent endovascular therapy in a single session between 2019 and 2021. Clinical and angiographic data was collected. Immediate occlusion and follow-up data were collected. Rankin modified scale was used for assessing clinical outcomes. Results: Twenty-five patients were treated, and fourteen had subarachnoid hemorrhage. Seventy-eight aneurysms were diagnosed, and 59 of them were treated. The most frequent location was at the ophthalmic segment. Maximum average height was 5.2- mm, which showed significant statistical difference with a ruptured condition (p≤0.02). The main modality for endovascular therapy was the remodeling technique, which was used in 39% of all cases. Immediate Raymond Roy staging was I in 60% of all cases, and IIIa in 35% of all cases. Complication rate was 24%, and mortality rate was 8%. Conclusions: Single session endovascular therapy is an effective and safe option for cases of multiple intracranial aneurysms in our institution. Occlusion and complication rates were acceptable.

Amyloid spell – A close mimic of transient ischemic attack!

Transient focal neurological episodes, also called amyloid spells occur as recurrent, transient episodes of spreading paresthesia seen in 14% of cerebral amyloid angiopathy (CAA) patients. An 81-year-old gentleman with coronary artery disease and a left ventricular clot was on anticoagulant treatment. He presented with three episodes of tingling in the left fingers spreading to the left arm and left leg, each lasting for 10 min. Magnetic resonance imaging of the brain with susceptibility imaging showed convexity hemorrhage, and curvilinear blooming in sulcal spaces of the right cerebral convexity and left precuneus. Warfarin was stopped. He was treated with clobazam, aspirin, and atorvastatin. He improved, so was discharged after 2 days. Amyloid spells can be confused with transient ischemic attack (TIA) or its mimics and the treatment given for TIA can lead to intracranial hemorrhage in CAA patients. Radiological features aid in the diagnosis of CAA and antiplatelets need to be administered cautiously in patients with suspected TIA.

A rare case of sulcal hemorrhage after ischemic stroke � A case report

Atraumatic Non-aneurysmal sulcal subarachnoid hemorrhage is very rare. Sulcal subarachnoid hemorrhage (sSAH) is characterized by isolated bleeding in one or a few adjacent sulci. Central sulcus hemorrhage is a rare imaging finding. There are many causes for sSAH. In older patients, sSAH is due to Cerebral Amyloid Angiopathy (CAA), while in younger patients, reversible cerebral vasoconstriction syndrome (RCVS) is the most frequent etiology. Imaging studies help in the evaluation of sSAH. We report a rare case of an isolated central sulcus hemorrhage on computed tomography. sSAH usually occur on the side with acute ischemic stroke, and it is unusual for sSAH to occur on the opposite side of the infarct territory, but in our case sSAH occurred on opposite side, but after a gap of 3 years.

Manejo ultra temprano del aneurisma cerebral roto. Reporte de caso y revisión de la literatura / Ultra-early management of ruptured brain aneurysm. A case report and literature review

Introducción : Los aneurismas intracraneales representan el 85% de casos de hemorragias subaracnoideas, dentro de las cuales las no traumáticas tienen una alta tasa de mortalidad (40-60%). En el manejo endovascular y microquirúrgico de esta enfermedad, el debate ha sido siempre intenso respecto a si el tratamiento temprano produce un beneficioso resultado funcional y reduce la morbi-mortalidad del paciente. Caso Clínico : Paciente mujer de 54 años, admitida con cefalea súbita y cuadro neurológico que cursó con rápido deterioro. La tomografía mostró hemorragia subaracnoidea por ruptura aneurísmica del complejo comunicante anterior; fue sometida a microcirugía dentro de las primeras 24 horas y transferida luego a UCI, sin complicaciones. Discusión : El tiempo de resolución, sea mediante clipaje microquirúrgico o tratamiento endovascular es tema de intensos debates. Las guías actuales señalan la necesidad del manejo más temprano posible de la patología. Conclusión : En nuestro caso, se obtuvo un buen resultado funcional debido a varios factores uno de ellos el ingreso precoz a cirugía. La actualización de las guías y nuevos estudios ayudarán a mejorar el conocimiento de la enfermedad y protocolos hospitalarios adecuados a la realidad clínica ayudarán a reducir su tiempo de resolución.

SUMMARY Introduction : Intracranial aneurysms account for 85% of all subarachnoid hemorrhages. Non-traumatic SAH has a high mortality rate (40-60%). Regarding the microsurgical and endovascular management for this pathology, there has been intense debate on whether early action is beneficial in terms of functional outcome and reduction of morbi-mortality. Clinical case : A 54-year-old woman admitted with a sudden, severe headache and a rapidly deteriorating neurological state at baseline, and with deterioration at the next hour. Tomography showed a subarachnoid hemorrhage due to ruptured aneurysm of the anterior communicating artery; the patient underwent surgery within the first 24 hours, with subsequent ICU management without complications. Discussion : The resolution time of this condition, either by micosurgery or endovascular management is a matter of intense debate. International guidelines point out the need of an earliest possible treatment. Conclusion : In our case, a good functional result was obtained due to several factors, one of which was early admission to surgery. The updating of guidelines and new studies will help to better understand the pathophysiology of SAH, and the creation of hospital protocols adapted to clinical realities will assist to reduce the resolution time of this pathology.

Role of temporary arterial occlusion in subarachnoid hemorrhage outcomes: a prospective cohort study

Purpose: Temporary arterial occlusion (TAO) is a widespread practice in the surgical treatment of intracranial aneurysms. This study aimed to investigate TAO's role during ruptured aneurysm clipping as an independent prognostic factor on short- and long-term outcomes. Methods: This prospective cohort included 180 patients with ruptured intracranial aneurysms and an indication of microsurgical treatment. Patients who died in the first 12 hours after admission were excluded. Results: TAO was associated with intraoperative rupture (IOR) (odds ratio ­ OR = 10.54; 95% confidence interval ­ 95%CI 4.72­23.55; p < 0.001) and surgical complications (OR = 2.14; 95%CI 1.11­4.07; p = 0.01). The group with TAO and IOR had no significant difference in clinical (p = 0.06) and surgical (p = 0.94) complications compared to the group that had TAO, but no IOR. Among the 111 patients followed six months after treatment, IOR, number of occlusions, and total time of occlusion were not associated with Glasgow Outcome Scale (GOS) in the follow-up (respectively, p = 0.18, p = 0.30, and p = 0.73). Among patients who underwent TAO, IOR was also not associated with GOS in the follow-up (p = 0.29). Conclusions: TAO was associated with IOR and surgical complications, being the latter independent of IOR occurrence. In long-term analysis, neither TAO nor IOR were associated with poor clinical outcomes.

Protective effects of histone deacetylase 6 specific inhibitor tubastatin A on subarachnoid hemorrhage in rats and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms.@*METHODS@#Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubAL group (giving 25 mg/kg TubA), and a SAH+TubAH group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery.@*RESULTS@#The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubAH group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubAL group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) .@*CONCLUSIONS@#HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.

Effects of ceftriaxone on Nrf2/GPX4 pathway and ferroptosis of cerebral cortex in early brain injury of rats with subarachnoid hemorrhage / 中华行为医学与脑科学杂志

Objective:To investigate the effects of ceftriaxone(CTX) on nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4) pathway and ferroptosis in early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Forty-eight clean grade male SD rats were randomly divided into sham operation group (Sham group), SAH group, SAH+ CTX group and SAH+ CTX+ Nrf2 inhibitor group (SAH+ CTX+ ML385 group) according to the random number table with 12 rats in each group.Seven days before modeling, rats in SAH+ CTX+ ML385 group were injected intraperitoneally with ML385 (30 mg · kg -1) once a day for consecutive 7 days.And 5 days before modeling, rats in SAH+ CTX group and SAH+ CTX+ ML385 group were treated with CTX(200 mg · kg -1) by intraperitoneal injection once a day for five consecutive days.Rats in Sham group and SAH group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution.After 24 hours of modeling, the neurological function score and brain tissue water content of rats in each group were measured.HE staining was used to observe the morphology of neurons in CA1 and CA3 regions of hippocampus.Prussian blue staining was used to observe the iron deposition in cerebral cortex.Spectrophotometer was used to determine the iron content, malonic dialdehyde(MDA) content, glutathione(GSH) content and GPX4 activity in cerebral cortex.Western blot was used to detect the expression levels of Nrf2 and GPX4 proteins in cerebral cortex.SPSS 23.0 was used for statistical analysis.One-way ANOVA was used to compare the mean of multiple groups of samples, and Dunnett- t test was used for further pairwise comparison between groups. Results:There was a statistically significant difference in the neurological function scores of rats in the four groups 24 hours after SAH ( F=48.40, P<0.001). The neurological function score of rats in the SAH group 24 hours after SAH was significantly lower than those in Sham group and SAH+ CTX group (both P<0.05). The brain water content of rats in the four groups 24 h after SAH was statistically significant ( F=49.61, P<0.001). The brain water content of rats in the SAH group 24 h after SAH was significantly higher than that in Sham group and SAH+ CTX group(both P<0.05). There was statistically significant differences in the number of neuronal necrosis in CA1 and CA3 regions of hippocampus in the four groups 24 hours after SAH ( F=17.44, 246.50, both P<0.001). The numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH group were significantly higher than those in Sham group and SAH+ CTX group, and the numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH+ CTX+ ML385 group were significantly higher than those in SAH+ CTX group (all P<0.05). Twenty-four hours after SAH, the amount of iron deposited in the cerebral cortex of rats in the four groups was statistically significant ( F=2 363.0, P<0.001). The iron deposition in the cerebral cortex of rats in the SAH group was significantly higher than those in Sham group and SAH+ CTX group (both P<0.05). There were significant differences in iron content, MDA content, GSH content and GPX4 activity in the cerebral cortex of the four groups 24 h after SAH( F=2 380.0, 1 322.0, 789.1, 815.5, all P<0.001). The content of iron and MDA in the cerebral cortex of rats in SAH group were significantly higher than those in Sham group, while the content of GSH and the activity of GPX4 were significantly lower than those in Sham group (all P<0.05). The content of iron and MDA in the cerebral cortex of rats in SAH+ CTX group were lower than those in SAH group, and the content of GSH and the activity of GPX4 were higher than those in SAH group (all P<0.05). At 24 h after SAH, the expression levels of Nrf2 and GPX4 protein in the cerebral cortex of the four groups were statistically significant ( F=888.7, 1 556.0, both P<0.001). The protein expression levels of Nrf2 (0.382±0.014) and GPX4 (0.329±0.019) in the cerebral cortex in SAH group were lower than those in Sham group ((0.746±0.009), (0.953±0.009)) (both P<0.05). The expression levels of Nrf2 (0.631±0.006) and GPX4 (0.833±0.008) protein in the cerebral cortex in the SAH+ CTX group were significantly higher than those in the SAH group (both P<0.05). The expression levels of Nrf2 (0.427±0.009) and GPX4 (0.525±0.011) protein in the cerebral cortex in SAH+ CTX+ ML385 group were significantly lower than those in SAH+ CTX group (both P<0.05). Conclusion:Ceftriaxone may inhibit ferroptosis during EBI in SAH rats by regulating Nrf2/GPX4 signal axis.

Effects of fasudil hydrochloride on ROCK2 protein and ferroptosis in hippocampus during early brain injury in rats with subarachnoid hemorrhage / 中华行为医学与脑科学杂志

Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.

A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage / 世界急诊医学杂志（英文）

@#BACKGROUND: A20 may be a neuroprotective factor. Herein, we aimed to investigate whether serum A20 levels were associated with disease severity, delayed cerebral ischemia (DCI), and outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this prospective cohort study containing 112 aSAH patients and 112 controls, serum A20 levels were quantified. At 90 d poststroke, Modified Rankin Scale (MRS) scores ≥3 were defined as a poor outcome. All correlations and associations were assessed using multivariate analysis. RESULTS: Compared with controls, there was a significant elevation of serum A20 levels in patients (median 123.7 pg/mL vs. 25.8 pg/mL; P<0.001). Serum A20 levels were independently correlated with Hunt-Hess scores (β 9.854; 95% confidence interval [95% CI] 2.481-17.227, P=0.009) and modified Fisher scores (β 10.349, 95% CI 1.273-19.424, P=0.026). Independent associations were found between serum A20 levels and poor outcome (odds ratio [OR] 1.015, 95% CI 1.000-1.031, P=0.047) and DCI (OR 1.018, 95% CI 1.001-1.035, P=0.042). Areas under the curve for predicting poor outcome and DCI were 0.771 (95% CI 0.682-0.845) and 0.777 (95% CI 0.688-0.850), respectively. Serum A20 levels ≥128.15 pg/mL predicted poor outcome, with a sensitivity of 73.9% and specificity of 74.2%, and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with 65.5% sensitivity and 89.2% specificity. Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores (both P>0.05). CONCLUSION: Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH, implying that serum A20 may be a potential prognostic biomarker for aSAH.

Role of SIRT1 in regulating endoplasmic reticulum stress in early brain injury after subarachnoid hemorrhage / 国际生物医学工程杂志

Objective:To investigate the effect of Sirtuin 1 (SIRT1) on subarachnoid hemorrhage (SAH) and its possible mechanism.Methods:A mouse model of SAH was constructed by internal carotid artery puncture. The protein and mRNA expression levels of SIRT1 at 0, 3, 6, 12, 24, 48, and 72 h were detected by Western Blot and qRT-PCR. A Western Blot assay was used to examine SIRT1 and the expression levels of endoplasmic reticulum stress-related markers GRP78, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP after administration of a SIRT1 inhibitor or SIRT1 si-RNA. At 24 h after SAH, subarachnoid hemorrhage volume, neurological function score, brain water content, and blood-brain barrier integrity were measured.Results:The highest expression of SIRT1 protein and mRNA was observed at 24 h compared with other time points, and the differences were statistically significant (all P < 0.001). Inhibition of SIRT1 expression leads to increased expression of endoplasmic reticulum stress-related proteins GRP78, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP, exacerbating hemorrhage and brain water content, disrupting blood-brain barrier integrity, and significantly reducing neurological function scores. Conclusions:Inhibition of SIRT1 expression significantly increased the endoplasmic reticulum response to excitation and exacerbated early brain injury after SAH.

Role of galectin-3 in the early brain injury of mice with subarachnoid hemorrhage is associated with the regulation of microglia polarization / 国际脑血管病杂志

Objective:To investigate the effect of galectin-3 (gal-3) on microglia polarization after subarachnoid hemorrhage (SAH).Methods:C57BL/6 male adult mice were used to induce SAH or sham operation models. Gal-3 siRNA or negative control siRNA was injected into the lateral ventricle 48 h before the model was induced. After 24 h of model preparation, the SAH score, neurological function score, brain water content, and Evans blue exudate were measured. Western blot analysis was used to detect the expressions of M1 phenotypic markers (inducible nitric oxide synthase [iNOS], CD11b, tumor necrosis factor [TNF]-α) and M2 phenotype markers (CD206, YM1/2, arginase-1 [Arg1]).Results:After using Gal-3 siRNA to inhibit Gal-3, the neurological function score significantly increased, while the SAH score, brain water content, and Evans blue exudate significantly decreased ( P<0.001). Western blot analysis showed that the expressions of M1 phenotypic markers (iNOS, CD11b and TNF-α) in microglia were significantly decreased after Gal-3 inhibition, while the expressions of M2 phenotypic markers (CD206, YM1/2 and Arg1) were significantly increased ( P<0.001). Conclusion:Inhibition of Gal-3 expression can alleviate the early brain injury after SAH, and its mechanism may be associated with regulating the polarization of microglia from M1 to M2 phenotype.

Predictors and prediction scores of shunt-dependent hydrocephalus in patients with aneurismal subarachnoid hemorrhage / 国际脑血管病杂志

Shunt-dependent hydrocephalus (SDHC) is a common and serious complication of aneurismal subarachnoid hemorrhage (aSAH). The incidence of SDHC after aSAH was 9%-36%, and it is associated with the poor outcome of patients. This article reviews the predictors and prediction scores of SDHC after aSAH.

Fatal intracranial bleedings in a viper bite: A case report / 中华创伤杂志(英文版)

Viper bite envenomation represents a significant occupational hazard among agricultural workers in India. The viper bite envenomation is usually suspected when a patient presents with predominant local symptoms at the bitten site, including pain, swelling, and necrosis. Further, systemic findings such as diffuse intravascular coagulation, hypotension, and shock may alert physicians of viper bite envenomation rather than a neurotoxic snake bite. However, cerebral complications are rare in viper bites but may potentially fatal. Central nervous system involvement in a viper bite is either due to neurotoxins or hemorrhagins present in the venom, which may induce cerebral thrombosis, ischemia, infarction, and hemorrhage. Here we present a case of a previously healthy adult male who succumbed to extensive subarachnoid, intracerebral, and intraventricular hemorrhages involving bilateral cerebral hemispheres following viper snake bite envenomation. This report highlights the importance of anticipating cerebral complications in viper bite envenomation, a rare occurrence. It also emphasizes the need for early antisnake venom administration to prevent and control systemic envenomation and its complications.

Braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in patients with unruptured complex intracranial aneurysms

Abstract Purposes: Braided and laser-cut stents both are efficacious and safe for coiling intracranial aneurysms. The study aimed to compare outcomes following braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in 266 patients who were diagnosed with unruptured intracranial aneurysms of different types and locations. Methods: Patients with unruptured complex intracranial aneurysms underwent braided (BSE cohort, n = 125) or laser engraved (LSE cohort, n = 141) stent-assisted embolization. Results: The deployment success rate was higher for patients of the LSE cohort than those of the BSE cohort (140 [99%] vs. 117 [94%], p = 0.0142). Seventy-one (fifty-seven percentages) and 73 (52%) were coil embolization procedure success rates of the BSE and the LSE cohorts. Periprocedural intracranial hemorrhage was higher in patients of the BSE cohort than those of the LSE cohort (8 [6%] vs. 1 [1%], p = 0.0142). Four (three percentages) patients from the LSE cohort and 3 (2%) patients from the BSE cohort had in-stent thrombosis during embolization. Permanent morbidities were higher in patients of the LSE cohort than those of the BSE cohort (8 [6%] vs. 1 [1%], p = 0.0389). Higher successful procedures (76% vs. 68%) and fewer postprocedural intracranial hemorrhage (0% vs. 5%) and mortality (0% vs. 5%) were reported for patients of the BSE cohort in posterior circulation aneurysmal location than those of the LSE cohort. Laser engraved stent has fewer problems with deployment and may have better periprocedural and follow-up outcomes after embolization. Conclusions: Braided stent-assisted embolization should be preferred when the aneurysm is present in the posterior circulation.

Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis

SUMMARY OBJECTIVE: The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage. METHODS: This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review. RESULTS: Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2). CONCLUSION: The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.