Nimodipine-associated standard dose reductions and neurologic outcomes after aneurysmal subarachnoid hemorrhage: the era of pharmacogenomics.

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.

Relationship Between Brain Tumors and Intracranial Aneurysms: A Systematic Review.

AIM: To investigate the possible relationship between intracranial aneurysms and brain neoplasms. MATERIAL AND METHODS: A comprehensive literature review involving a search of the databases PubMed and Embase to identify relevant articles was conducted in March 2021. The initial search retrieved 451 articles. After deduplication and screening of abstracts, 56 articles were selected. After reading of the full texts, 19 articles were included in the review. RESULTS: There insufficient evidence to support that people with brain neoplasms have a higher incidence rate of IAs. However, the prevalence of IAs appears to be higher in patients with pituitary tumors than in the general population. The key factors affecting prognosis were tumor type in patients with unruptured aneurysms and progression of subarachnoid hemorrhage in individuals with ruptured aneurysms. Treatment should be individualized according to patient age, tumor pathology, location, and aneurysm rupture risk. CONCLUSION: There is a lack of evidence to affirm that the existence of brain neoplasm plays a role in the formation and rupture of intracranial aneurysms. Additionally, there is insufficient evidence to confirm a greater prevalence of intracranial aneurysms in individuals with brain tumors. The association of these two disorders does not appear to worsen patient outcome. Prognosis depends on tumor pathology for malignant cases and on subarachnoid hemorrhage in patients with ruptured aneurysms.

The relationship between the level of vitamin D and ruptured intracranial aneurysms among patients with high sun exposure.

Non-traumatic subarachnoid hemorrhage (SAH) accounts for 3-5% of acute strokes. Intracranial aneurysm is the most common cause of non-traumatic SAH. Vitamin D influences the cardiovascular system, including the formation and rupture of cerebral aneurysms. To evaluate the serum vitamin D level in patients living in the tropical zone who suffered aneurysmal subarachnoid hemorrhage and its correlation with demographic and neurological characteristics. This is an analytical cross-sectional study to assess the serum level of vitamin D in a study population of 99 patients treated and diagnosed with aSAH in a public hospital in Recife-PE over a period of 12 months. In the study sample, composed of individuals with high sun exposure due to the lifestyle they lead in a tropical region, we observed hypovitaminosis D (85.9%), with a median of 19.9 ng/ml, although the majority of individuals are skin with high concentration of melanin (Fitzpatrick skin type IV and V). In addition, rates of sun exposure are high to all patients (Solar Index 9.03 P50). Most individuals were female (79.8%); there was no statistical difference in solar exposure/solar index between genders. As for the neurological repercussions, there was no statistical relevance in the clinical prognostic scales evaluated. As the sample was composed mainly of individuals whose economic activity is agriculture, the values of solar index found are vastly higher than those of other studies conducted in high latitude regions. In line with the literature review, some aspects were raised with the objective of justifying such findings that go from the base of the poor diet of these individuals, the increase of melanin in the skin and genetic alterations that directs us to possible mechanisms of natural photoprotection to high sun exposure. Thus, we had a vast majority (85%) of hypovitaminosis D, which in fact makes us wonder if there is any influence of calcitriol on vitamin D receptors in vascular walls and in the cardiovascular system as a whole, which influence bleeding events of this nature. As for the neurological repercussions, measured using assessment scales (Glasgow coma scale, WFNS scale, Hunt-Hess and Fisher's tomographic scale) there was no significant difference in the results. As it is only a descriptive study, the causal relationship of the facts cannot be established. However, in a population exposed to high sun exposure and affected by aneurysmal SAH, there is a significant rate of hypovitaminosis D, which supports the hypothesis that vitamin D plays a role in vascular pathologies, such as cerebral aneurysms and SAH.

Prognostic value of scales for aneurysmal subarachnoid hemorrhage: Report of a reference center in Peru.

INTRODUCTION: Multiple scales have been designed to stratify the severity and predict the prognosis in the initial evaluation of patients with aneurysmal subarachnoid hemorrhage (aSAH). Our study aimed to validate the most commonly used prognostic scales for aSAH in our population: Hunt-Hess, modified Hunt-Hess, World Federation of Neurosurgical Societies (WFNS), Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage (PAASH), and Barrow Aneurysm Institute (BAI) scales. METHODS: This study includes all aSAH cases treated at our institution between June 2019 and December 2020. We developed a retrospective cohort by reviewing medical records and radiologic images performed during hospitalization. The outcome was evaluated using the modified Rankin scale (mRS). It was defined as a poor outcome (mRS 4-5) and mortality (mRS 6). The ROC curves and the area under the curve (AUC) of each of the prognostic scales were calculated to evaluate their prognostic prediction capacity. RESULTS: A total of 142 patients were diagnosed with aSAH. A poor outcome occurred in 52.1% of the patients, whereas mortality was 27.5%. The AUC of the scales studied was similar and no significant difference was found between them for predicting a poor outcome (P = .709) or mortality (P = .715). CONCLUSION: We determined that the prognostic scales for aSAH had a similar predictive value for poor clinical outcomes and mortality in our institution, with no significant difference. Thus, we recommend the most simple and well-known scale used institutionally.

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 4.72-23.55; p < 0.001) and surgical complications (OR = 2.14; 95%CI 1.11-4.07; 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.

Correlation between tomographic scales and vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

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.

Complicaciones del tratamiento endovascular y quirúrgico en las hemorragias subaracnoideas aneurismáticas en Uruguay: análisis prospectivo de una serie de 211 casos / Complications of endovascular and surgical treatment in aneurysmal subarachnoid hemorrhages in Uruguay prospective analysis of a series of 211 cases / Complicações do tratamento endovascular e cirúrgico nas hemorragias subaracnóideas aneurismais no Uruguai: análise prospectiva de uma série 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.

Predestinative role acidic cerebrospinal fluid on the destiny of central channel in spinal cord following subarachnoid hemorrhage: an experimental study.

OBJECTIVE: Acidosis is the most dangerous complication in subarachnoid hemorrhage (SAH). This study aimed to investigate the effect of acidic cerebrospinal fluid on central canal structures after SAH. MATERIALS AND METHODS: Twenty-eight hybrid rabbits were studied. Blood and cerebrospinal fluid pH values were recorded before/during/after the experimental procedures. The structures related to the central canals at the level of C5 of the cervical spinal cord were then examined histopathologically. The relationship between pH values of ependymal cells and degenerated epithelial cell densities was statistically analyzed. RESULTS: Mean blood pH values and degenerated ependymal cell density (n/mm2) were as follows: 7.351 ± 0.033/23 ± 7 in control, 7.322 ± 0.059/78 ± 13 in SHAM, and 7.261 ± 0.048/254 ± 62 in study animals. Gross examinations revealed swelling, edema, pia-arachnoid adhesions, ventral canal dilatation, arachnoiditis, central canal hemorrhage, occlusions, and dilatation in the spinal cord. CONCLUSION: Cerebrospinal fluid acidosis-induced central channel pathologies should be considered an important complication of SAH following SAH.

OBJETIVO: La acidosis es la complicación más peligrosa en la hemorragia subaracnoidea (HSA). El objetivo de este estudio fue investigar el efecto del líquido cefalorraquídeo ácido en las estructuras del canal central tras la HSA. MATERIALES Y MÉTODOS: Se estudiaron 28 conejos híbridos. Se registraron los valores de pH de la sangre y del líquido cefalorraquídeo antes, durante y después de los procedimientos experimentales. A continuación se examinaron histopatológicamente las estructuras relacionadas con los canales centrales a nivel de C5 de la médula espinal cervical. Se analizó estadísticamente la relación entre los valores de pH de las células ependimarias y las densidades de células epiteliales degeneradas. RESULTADOS: Los valores medios de pH en sangre y la densidad de células ependimarias degeneradas (n/mm2) fueron los siguientes: 7.351 ± 0.033/23 ± 7 en el control, 7.322 ± 0.059/78 ± 13 en el SHAM, 7.261 ± 0.048/254 ± 62 en los animales del estudio. Los exámenes macroscópicos revelaron hinchazón, edema, adherencias pia-aracnoideas, dilatación del canal ventral, aracnoiditis, hemorragia del canal central, oclusiones y dilatación en la médula espinal. CONCLUSIONES: Las patologías del canal central inducidas por la acidosis del líquido cefalorraquídeo deben considerarse como una complicación importante de la HSA tras una hemorragia subaracnoidea.

Multimodal monitoring intracranial pressure by invasive and noninvasive means.

Although the placement of an intraventricular catheter remains the gold standard method for the diagnosis of intracranial hypertension (ICH), the technique has several limitations including but not limited to its invasiveness. Current noninvasive methods, however, still lack robust evidence to support their clinical use. We aimed to estimate, as an exploratory hypothesis generating analysis, the discriminative power of four noninvasive methods to diagnose ICH. We prospectively collected data from adult intensive care unit (ICU) patients with subarachnoid hemorrhage (SAH), intraparenchymal hemorrhage (IPH), and ischemic stroke (IS) in whom invasive intracranial pressure (ICP) monitoring had been placed. Measures were simultaneously collected from the following noninvasive methods: optic nerve sheath diameter (ONSD), pulsatility index (PI) using transcranial Doppler (TCD), a 5-point visual scale designed for brain Computed Tomography (CT), and two parameters (time-to-peak [TTP] and P2/P1 ratio) of a noninvasive ICP wave morphology monitor (Brain4Care[B4c]). ICH was defined as a sustained ICP > 20 mmHg for at least 5 min. We studied 18 patients (SAH = 14; ICH = 3; IS = 1) on 60 occasions with a mean age of 52 ± 14.3 years. All methods were recorded simultaneously, except for the CT, which was performed within 24 h of the other methods. The median ICP was 13 [9.8-16.2] mmHg, and intracranial hypertension was present on 18 occasions (30%). Median values from the noninvasive techniques were ONSD 4.9 [4.40-5.41] mm, PI 1.22 [1.04-1.43], CT scale 3 points [IQR: 3.0], P2/P1 ratio 1.16 [1.09-1.23], and TTP 0.215 [0.193-0.237]. There was a significant statistical correlation between all the noninvasive techniques and invasive ICP (ONSD, r = 0.29; PI, r = 0.62; CT, r = 0.21; P2/P1 ratio, r = 0.35; TTP, r = 0.35, p < 0.001 for all comparisons). The area under the curve (AUC) to estimate intracranial hypertension was 0.69 [CIs = 0.62-0.78] for the ONSD, 0.75 [95% CIs 0.69-0.83] for the PI, 0.64 [95%Cis 0.59-069] for CT, 0.79 [95% CIs 0.72-0.93] for P2/P1 ratio, and 0.69 [95% CIs 0.60-0.74] for TTP. When the various techniques were combined, an AUC of 0.86 [0.76-0.93]) was obtained. The best pair of methods was the TCD and B4cth an AUC of 0.80 (0.72-0.88). Noninvasive technique measurements correlate with ICP and have an acceptable discrimination ability in diagnosing ICH. The multimodal combination of PI (TCD) and wave morphology monitor may improve the ability of the noninvasive methods to diagnose ICH. The observed variability in non-invasive ICP estimations underscores the need for comprehensive investigations to elucidate the optimal method-application alignment across distinct clinical scenarios.

Hemorragia subaracnoidea asociada a aneurisma cerebral con malformación arteriovenosa / Subarachnoid hemorrhage related to a cerebral aneurysm with arteriovenous malformation

Los aneurismas asociados a las malformaciones arteriovenosas son lesiones vasculares que suelen encontrarse hasta en el 15 % de los pacientes que las presentan, lo que incrementa el riesgo global de hemorragia. Se presenta una paciente de 53 años de edad que sufrió un cuadro agudo de hemorragia subaracnoidea; en el estudio se evidenció la presencia de un aneurisma de comunicante anterior y malformación arteriovenosa distal de la arteria cerebral anterior izquierda, el cual requirió procedimiento quirúrgico debido al sangramiento. La evolución de la paciente fue satisfactoria y sin complicaciones.

Aneurysms associated with arteriovenous malformations are vascular lesions that are usually found in up to 15% of the patients who present them, which increases the overall risk of bleeding. We present a 53-year-old female patient who suffered from an acute subarachnoid hemorrhage; the study revealed the presence of an anterior communicating aneurysm and a distal arteriovenous malformation of the left anterior cerebral artery, which required surgical procedure due to bleeding. The evolution of the patient was satisfactory and without complications.

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.

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.

Efficacy and Safety of Clazosentan After Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. METHODS: Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. RESULTS: Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). CONCLUSION: Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.

Research trends within aneurysmal subarachnoid hemorrhage from 2017 to 2021: a bibliometric study.

Bibliometric analyses are a well-established strategy for understanding the dynamics of publications. Aneurysmal subarachnoid hemorrhage (aSAH) is a hot topic in neurology and neurosurgery research. To perform a bibliometric analysis of recent publications within aSAH. Articles addressing aSAH published between 2017 and 2021 were included and had their information extracted from Scopus. A total of 2177 articles were included. The mean number of citations was 6.18 (95%CI = 5.77-6.59). 2021 and 2020 were the most prolific years. World Neurosurgery (N = 389/2,177 articles; 17,87%) was the leading publisher, and American Journal of Neuroradiology had the highest number of citations per article (14.82) among journals with ≥ 10 publications. Primary research (N = 1624/2177) predominated, followed by case reports (N = 434/2,177). Among secondary studies, systematic reviews (N = 78/119) surpassed narrative reviews (N = 41/119). USA led the number of publications (N = 548/2,177 articles; 25.17%), followed by China (N = 358/2,177 articles; 16.44%). High-income countries had a higher number of publications (N = 1624/2177) and more citations per article (6.84) than middle-income countries (N = 553/2177 and 4.25, respectively). There were zero articles from low-income countries. European and North American institutions had the greatest research impact. There was an increase in the number of published articles in the last few years (2020 and 2021). Many studies had a low level of evidence, whereas interventional studies were uncommon.

Prospective Analysis of Cerebral Edema Admission and Clinical Outcome in Ruptured Intracranial Aneurysm.

AIM: To evaluate the association between global cerebral edema (GCE) after subarachnoid hemorrhage (SAH) and its impact on functional outcome evaluated by the modified Rankin scale (mRS). MATERIAL AND METHODS: This is a prospective cohort study with patients who were admitted to the hospital due to SAH. During the period from January 2018 to November 2019, 107 patients with intracranial aneurysms were enrolled. Using univariate and multivariate analysis, we sought to identify predictors and evaluated the impact of GCE on outcome after 6 months using the mRS. RESULTS: GCE was present in 54 (50.5%) patients, of which 27 (25.2%) were mild, 20 (18.7%) moderate and 7 (6.5%) were severe. Univariate analysis identified high Hunt-Hess and Glasgow coma scale on clinical admission as predictors factors of GCE (p < 0.05), and higher modified Fisher scale as a radiological predictor of Glasgow coma scale (p < 0.05). Thirty-three (30.8%) patients were deceased at 6 months. Death or severe disability were predicted by higher age, poor clinical scale on admission and severe GCE (p < 0.05). CONCLUSION: GCE on admission is independently associated with poor clinical outcomes at discharge, and six months after SAH. Given its strong association with poor clinical grade on admission, GCE should be considered a straightforward and radiological important marker of early brain injury, with ominous implications.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and prognosis after aneurysmal subarachnoid hemorrhage: a cohort study.

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.

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.

Effect of an Albumin Infusion Treatment Protocol on Delayed Cerebral Ischemia and Relevant Outcomes in Patients with Subarachnoid Hemorrhage.

BACKGROUND: An institutional management protocol for patients with subarachnoid hemorrhage (SAH) based on initial cardiac assessment, permissiveness of negative fluid balances, and use of a continuous albumin infusion as the main fluid therapy for the first 5 days of the intensive care unit (ICU) stay was implemented at our hospital in 2014. It aimed at achieving and maintaining euvolemia and hemodynamic stability to prevent ischemic events and complications in the ICU by reducing periods of hypovolemia or hemodynamic instability. This study aimed at assessing the effect of the implemented management protocol on the incidence of delayed cerebral ischemia (DCI), mortality, and other relevant outcomes in patients with SAH during ICU stay. METHODS: We conducted a quasi-experimental study with historical controls based on electronic medical records of adults with SAH admitted to the ICU at a tertiary care university hospital in Cali, Colombia. The patients treated between 2011 and 2014 were the control group, and those treated between 2014 and 2018 were the intervention group. We collected baseline clinical characteristics, cointerventions, occurrence of DCI, vital status after 6 months, neurological status after 6 months, hydroelectrolytic imbalances, and other SAH complication. Multivariable and sensitivity analyses that controlled for confounding and considered the presence of competing risks were used to adequately estimate the effects of the management protocol. The study was approved by our institutional ethics review board before study start. RESULTS: One hundred eighty-nine patients were included for analysis. The management protocol was associated with a reduced incidence of DCI (hazard ratio 0.52 [95% confidence interval 0.33-0.83] from multivariable subdistribution hazards model) and hyponatremia (relative risk 0.55 [95% confidence interval 0.37-0.80]). The management protocol was not associated with higher hospital or long-term mortality, nor with a higher occurrence of other unfavorable outcomes (pulmonary edema, rebleeding, hydrocephalus, hypernatremia, pneumonia). The intervention group also had lower daily and cumulative administered fluids compared with historic controls (p < 0.0001). CONCLUSIONS: A management protocol based on hemodynamically oriented fluid therapy in combination with a continuous albumin infusion as the main fluid during the first 5 days of the ICU stay appears beneficial for patients with SAH because it was associated with reduced incidence of DCI and hyponatremia. Proposed mechanisms include improved hemodynamic stability that allows euvolemia and reduces the risk of ischemia, among others.

Effects of Tranexamic Acid in Patients with Subarachnoid Hemorrhage in Brazil: A Prospective Observational Study with Propensity Score Analysis.

BACKGROUND: Rebleeding from a ruptured aneurysm increases the risk of unfavorable outcomes after subarachnoid hemorrhage (SAH) and is prevented by early aneurysm occlusion. The role of antifibrinolytics before aneurysm obliteration remains controversial. We investigated the effects of tranexamic acid on long-term functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: This was a single-center, prospective, observational study conducted in a high-volume tertiary hospital in a middle-income country from December 2016 to February 2020. We included all consecutive patients with aSAH who either received or did not receive tranexamic acid (TXA) treatment. Multivariate logistic regression analysis using propensity score was used to evaluate the association of TXA use with long-term functional outcomes, measured by the modified Rankin Scale (mRS) at 6 months. RESULTS: A total of 230 patients with aSAH were analyzed. The median (interquartile range) age was 55 (46-63) years, 72% were women, 75% presented with good clinical grade (World Federation of Neurological Surgeons grade 1-3), and 83% had a Fisher scale of 3 or 4. Around 80% of patients were admitted up to 72 h from ictus. The aneurysm occlusion method was surgical clipping in 80% of the patients. A total of 129 patients (56%) received TXA. In multivariable logistic regression using inverse probability treatment weighting, the long-term rate of unfavorable outcomes (modified Rankin scale 4-6) was the same in the TXA and non-TXA groups (61 [48%] in TXA group vs. 33 [33%] in non-TXA group; odds ratio [OR] 1.39, 95% confidence interval [CI] 0.67-2.92; p = 0.377). The TXA group had higher in-hospital mortality (33 vs. 11% in non-TXA group; OR 4.13, 95% CI 1.55-12.53, p = 0.007). There were no differences between the groups concerning intensive care unit length of stay (16 ± 11.22 days in TXA group vs. 14 ± 9.24 days in non-TXA group; p = 0.2) or hospital (23 ± 13.35 days in TXA group vs. 22 ± 13.36 days in non-TXA group; p = 0.9). There was no difference in the rates of rebleeding (7.8% in TXA group vs. 8.9% in non-TXA group; p = 0.31) or delayed cerebral ischemia (27% in TXA group vs. 19% in non-TXA group; p = 0.14). For the propensity-matched analysis, 128 individuals were selected (64 in TXA group and 64 in non-TXA group), and the rates of unfavorable outcomes at 6 months were also similar between groups (45% in TXA group and 36% in non-TXA group; OR 1.22, 95% CI 0.51-2.89; p = 0.655). CONCLUSIONS: Our findings in a cohort with delayed aneurysm treatment reinforce previous data that TXA use before aneurysm occlusion does not improve functional outcomes in aSAH.

Utility of transcranial color-coded duplex sonography in diagnosis and monitoring of PICA aneurysm in subarachnoid hemorrhage.

This case describes the successful use of transcranial color-coded duplex sonography (TCCD) to diagnose a posterior circulation aneurysm in a patient with subarachnoid hemorrhage. A 33-year-old, was admitted to the ICU after a brain CT scan showed peritroncal subarachnoid hemorrhage. TCCD revealed a rounded image with color Doppler near the P1 portion of the right posterior cerebral artery, which was later confirmed to be a 4 mm aneurysm at the right posterior inferior cerebellar artery (PICA). The aneurysm was treated with coil exclusion and TCCD confirmed its disappearance post-treatment. While TCCD has limitations, including its inability to detect small aneurysms, it is a noninvasive diagnostic tool that provides real-time visualization of the brain and allows for follow-up evaluations. This case demonstrates the potential usefulness of TCCD in diagnosing cerebral aneurysms in patients with subarachnoid hemorrhage and for follow-up evaluations post-treatment.