World Federation Of Neurological Surgeons Research Articles

Factores asociados a una evolución desfavorable en la hemorragia subaracnoidea aneurismática. Serie de 334 pacientes

ObjectiveThis study evaluates care-related sociodemographic, clinical, and imaging factors and influences associated with outcome at discharge in patients with aneurismal subarachnoid haemorrhage. Patients and methodRetrospective cohort study in 334 patients treated at Hospital Hermanos Ameijeiras in Havana, Cuba between October 2005 and June 2014. ResultsLogistic regression analysis determined that the following factors were associated with higher risk of poor outcome: age older than 65 years (OR 3.51, 95% CI 1.79-5.7, P=.031), female sex (OR 2.17, 95% CI 1.22-3.84, P=.0067), systolic hypertension (OR 4.82, 95% CI 2.27-9.8, P=.0001), and hyperglycaemia at admission (OR 3.93, 95% CI 2.10-7.53, P=.0003). Certain complications were also associated with poor prognosis, including respiratory infection (OR 2.73, 95% CI 1.27-5.85, P=.0085), electrolyte disturbances (OR 3.33, 95% CI 1.33-8.28, P=.0073), hydrocephalus (OR 2.21, 95% CI 1.05-4.63, P=.0039), rebleeding (OR 16.50, 95% CI 8.24-41.24, P=.0000), symptomatic vasospasm (OR 19.00, 95% CI 8.86-41.24, P=.0000), cerebral ischaemia (OR 3.82, 95% CI 1.87-7.80, P=.000) and multiplex rebleeding (OR 6.69, 95% CI 1.35-36.39, P=.0019). Grades of iii and iv on the World Federation of Neurological Surgeons (OR 2.09, 95% CI 1.12-3.91, P=.0021) and Fisher scales (OR 5.18, 95% CI 2.65-10.29, P=.0008) were also related to poor outcome. ConclusionsOutcome of aneurysmal subarachnoid haemorrhage was related to age, sex, clinical status at admission to the stroke unit, imaging findings according to the Fisher scale, blood pressure, glycaemia and such complications as electrolyte disturbances, hydrocephalus, rebleeding, and multiplex rebleeding.

Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy.

Background. Treatment of symptomatic delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is difficult. Recent studies suggest intravenous (IV) high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS) clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

Critical age affecting 1-year functional outcome in elderly patients aged ≥ 70 years with aneurysmal subarachnoid hemorrhage.

While advanced age is already recognized as an independent risk factor for a poor functional outcome following an aneurysmal subarachnoid hemorrhage (SAH), it is also important to investigate the critical age for defining a higher risk population among elderly patients and the clinical grade at admission in order to provide a prognostic description and help guide the management of patients aged ≥ 70 years. This retrospective study included 165 patients aged 70-90 years who underwent surgical or endovascular treatment for a ruptured aneurysm. In addition to medical and radiological data, telephone interviews were used to obtain the 1-year functional outcome. A multivariate analysis revealed age (p = 0.001) and the World Federation of Neurological Surgeons (WFNS) grade (p = 0.001), regardless of the treatment modalities (surgical versus endovascular), as significant risk factors for a poor outcome, while a receiver operating characteristic analysis revealed 75 years as an appropriate cutoff value for the patient age to predict a poor 1-year functional outcome (area under the curve: 0.683). For the patients aged 70-75 years with good (1-3) and poor (4-5) WFNS grades, 81.9 % and 42.9 % achieved a favorable outcome (modified Rankin Scale 0-3), respectively, whereas for the patients over the critical age (> 75 years) with good and poor WFNS grades, 54.8 % and 5.9 % achieved a favorable outcome, respectively. The long-term outcome for elderly patients with an aneurysmal SAH is affected primarily by the clinical condition at admission and the patient's age in relation to the critical age (> 75 years), regardless of the treatment modalities, including surgical clipping and endovascular coiling.

Circulating levels of neuropeptide proenkephalin A predict outcome in patients with aneurysmal subarachnoid hemorrhage

High plasma proenkephalin A level has been associated with ischemic stroke severity and clinical outcomes. This study aimed to assess the relationship between proenkephalin A and disease severity as well as to investigate its ability to predict long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. Plasma proenkephalin A concentrations of one hundred and eighty patients and 180 sex- and age-matched healthy controls were measured by chemoluminescence sandwich immunoassay. Plasma proenkephalin A level was substantially higher in patients than in healthy controls (205.5±41.6pmol/L vs. 90.8±21.1pmol/L, P<0.001), was highly associated with World Federation of Neurological Surgeons (WFNS) score (r=0.470, P<0.001) and Fisher score (r=0.488, P<0.001), was an independent predictor for 6-month mortality [odds ratio (OR), 1.183; 95% confidence interval (CI), 1.067–1.339; P=0.004] and unfavorable outcome (Glasgow Outcome Scale score of 1–3) (OR, 1.119; 95% CI, 1.046–1.332; P=0.005) using multivariate analysis, and had high area under receiver operating characteristic curve (AUC) for prediction of 6-month mortality (AUC, 0.831; 95% CI, 0.768–0.883) and unfavorable outcome (AUC, 0.821; 95% CI, 0.757–0.874). The predictive value of the plasma proenkephalin A concentration was also similar to those of WFNS score and Fisher score (both P>0.05). In a combined logistic-regression model, proenkephalin A improved the AUCs of WFNS score and Fisher score, but the differences were not significant (both P>0.05). Thus, proenkephalin A level may be a useful, complementary tool to predict mortality and functional outcome at 6 months after aneurysmal subarachnoid hemorrhage.

The clinical profile, management, and overall outcome of aneurysmal subarachnoid hemorrhage at the neurosurgical unit of a tertiary care center in India.

Background and Purpose:Several studies report good outcomes in selected patients of aneurysmal subarachnoid hemorrhage (aSAH). The purpose of our study is to project the clinical characteristics, management, and overall outcome of patients with aSAH presenting to a tertiary care center in India.Materials and Methods:A prospective study was conducted over a period of 10 months and all patients presenting with aSAH were studied. Patients presenting in all grades and managed with any type of intervention or managed conservatively were included to characterize their clinical and radiological profile at admission, during management, and at discharge. Outcome was assessed with the Glasgow Outcome Score (GOS) at 3 months follow-up.Results:Out of the 482 patients [mean age: 51.3 (±13.5); M: F = 1:1], 330 patients were fit to be taken up for intervention of the ruptured aneurysm, while 152 patients were unfit for any intervention. At 3 months follow-up, good outcome (GOS 4 and 5) was observed in 159 (33%), poor outcome (GOS 2 and 3) in 53 (11%), and death in 219 (45.4%) patients, while 51 patients (10.6%) were lost to follow-up. Most (95%) of the patients in the non-intervention group expired, and hence the high mortality rate, as we have analyzed the results of all patients of all grades, regardless of the treatment given. The predictors of poor outcome (GOS 1, 2, and 3) at 3 months follow-up, using multinomial regression model, were: World Federation of Neurological Surgeons (WFNS) grade IV and V (at admission and after adequate resuscitation) [odds ratio (OR): 35.1, 95% confidence interval (CI): 10.8-114.7] and presence of hypertension as a co-morbid illness [OR: 2.7, 95% CI: 1.6-5.6]. All patients showing acute infarction on computed tomography scan at presentation had a poor outcome.Conclusions:Despite recent advances in the treatment of patients with aSAH, the morbidity and mortality rates have failed to improve significantly in unselected patients and natural cohorts. This may be attributed to the natural history of aSAH, and calls for new strategies to diagnose and treat such patients before the catastrophe strikes.

80歳以上の破裂脳動脈瘤の治療成績

While the number of elderly patients who presented with aneurysmal subarachnoid hemorrhage (SAH) has been increasing, its optimal management in that population remains controversial. Therefore, we retrospectively reviewed the treatment outcomes in 49 consecutive patients aged between 80 and 94 years who presented with SAH. The neurological World Federation of Neurological Surgeons (WFNS) grade at the time of admission was Grade I in 7, Grade II in 11, Grade III in 8, Grade IV in 13, and Grade V in 10 patients. Of the 49 patients, 28 underwent coil embolization, and 7 (25%) had a favorable outcome (mRS: 0–2) at discharge, while in 21 (75%) the outcome was poor (mRS: 3–6). Six patients underwent clipping; the outcome was favorable in one patient (17%) and poor in 5 (83%). Of 15 patients under conservative therapy none had a favorable outcome. A low WFNS grade (I–II) was significantly associated with a favorable outcome (p＜0.05). Although the treatment outcome in elderly patients with SAH was poor, radical treatment of ruptured aneurysms should be considered if their WFNS grade is low.

Is aneurysm repair justified for the patients aged 80 or older after aneurysmal subarachnoid hemorrhage?

BackgroundWith the advancement of an aging society in the world, an increasing number of elderly patients have been hospitalized due to aneurysmal subarachnoid hemorrhage (aSAH). There is no study that...

Cerebral Lactate Correlates with Early Onset Pneumonia after Aneurysmal SAH

Pneumonia is a significant medical complication following aneurysmal subarachnoid hemorrhage (aSAH). The aSAH may initiate immune interactions leading to depressed immunofunction, followed by an increased risk of infection. It remains unclear as to whether there is a possible association between cerebral metabolism and infections. Clinical and microdialysis data from aSAH patients prospectively included in the CoOperative Study on Brain Injury Depolarisations protocol Berlin were analyzed. Levels of glucose, lactate, pyruvate, and glutamate were measured hourly using microdialysis in the cerebral extracellular fluid. The occurrence of pneumonia (defined by positive microbiological cultures) and delayed ischemic neurological deficits (DIND) was documented prospectively. Eighteen aSAH patients (52.7 ± 10.7 years), classified according to the World Federation of Neurological Surgeons in low (I-III, n = 9) and high (IV-V, n = 9) grades, were studied. Eight patients (45%) experienced DIND, 10 patients (56%) pneumonia (mean onset day 2.6). Lactate was elevated at day 3 in infected patients (n = 9, median = 6.82 mmol/L) vs. patient without infections (n = 6, median = 2.90 mmol/L, p = 0.036). The optimum cut-off point to predict pneumonia at day 3 was 3.57 mmol/L with a sensitivity of 0.77, and a specificity of 0.66 (area under curve was 0.833 with p = 0.034). Lactate at day 7 was higher in DIND patients compared to no-DIND-patients (p = 0.016). Early elevated lactate correlated with occurrence of bacterial pneumonia, while late elevations with DIND after aSAH. Future investigations may elucidate the relationship between cerebral lactate and markers of immunocompetence and more detailed to identify patients with higher susceptibility for infections.

Plasma visfatin, a possible prognostic marker in aneurysmal subarachnoid hemorrhage

Visfatin is linked to inflammation and associated with clinical outcomes of intracerebral hemorrhage. This study was designed to investigate whether visfatin might serve as a marker of severity and prognosis in aneurysmal subarachnoid hemorrhage. In this study, plasma visfatin levels of 172 consecutive patients and 172 sex and age-matched healthy subjects were determined using enzyme-linked immunosorbent assay. The recorded clinical outcomes included in-hospital mortality and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1–3). Plasma visfatin level was substantially higher in patients than in healthy controls (92.1±20.5ng/mL vs. 12.4±3.2ng/mL; P<0.001), was significantly associated with the World Federation of Neurological Surgeons (WFNS) score (r=0.569, P<0.001) and Fisher score (r=0.657, P<0.001), was an independent predictor of in-hospital mortality [odds ratio (OR), 1.378; 95% confidence interval (CI), 1.036–1.866; P=0.002] and 6-month mortality (OR, 1.261; 95% CI, 1.018–1.745; P=0.004) and unfavorable outcome (OR, 1.207; 95% CI, 1.012–1.682; P=0.008) in multivariate logistic regression analysis and had high predictive value for in-hospital mortality [area under curve (AUC), 0.849; 95% CI, 0.787–0.899; P<0.001] and 6-month mortality (AUC, 0.868; 95% CI, 0.808–0.915; P<0.001) and unfavorable outcome (AUC, 0.859; 95% CI, 0.797–0.907; P<0.001) using receiver operating characteristic curves. AUCs of visfatin were similar to those of WFNS score and Fisher score (all P>0.05), but visfatin did not improve the predictive values of WFNS score and Fisher score (all P>0.05). Thus, visfatin may be associated with clinical severity of aneurysmal subarachnoid hemorrhage and also have prognostic value for clinical outcomes.

The SAH Score: A Comprehensive Communication Tool

The Hunt and Hess grade and World Federation of Neurological Surgeons (WFNS) scale are commonly used to predict mortality after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to improve the accuracy of mortality prediction compared with the aforementioned scales by creating the "SAH score." The aSAH database at our institution was analyzed for factors affecting in-hospital mortality using multiple logistic regression analysis. Scores were weighted based on relative risk of mortality after stratification of each of these variables. Glasgow Coma Scale (GCS) was subdivided into groups of 3-4 (score=1), 5-8 (score=2), 9-13 (score=3), and 14-15 (score=4). Age was categorized into 4 subgroups: 18-49 (score=1), 50-69 (score=2), 70-79 (score=3), and 80 years or more (score=4). Medical comorbidities were subdivided into none (score=1), 1 (score=2), or 2 or more (score=3). In total, 1134 patients were included; all-cause SAH hospital mortality was 18.3%. Admission GCS, age, and medical comorbidities significantly affected mortality after multivariate analysis (P<.05). Summated scores ranged from 0 to 8 with escalating mortality at higher scores (0=2%, 1=6%, 2=8%, 3=15%, 4=30%, 5=58%, 6=79%, 7=87%, and 8=100%). Positive predictive value (PPV) for scores in the range 7-8 was 88.5%, whereas 6-8 was 83%. Negative predictive value (NPV) was 94% for range 0-2 and 92% for 0-3. The area under the curve (AUC) for the SAH score was .821 (good accuracy), compared with the WFNS scale (AUC .777, fair accuracy) and the Huntand Hess grade (AUC .771, fair accuracy). The SAH score was found to be more accurate in predicting aSAH mortality compared with the Hunt and Hess grade and WFNS scale.

Heart-fatty acid-binding and tau proteins relate to brain injury severity and long-term outcome in subarachnoid haemorrhage patients

BackgroundVasospasm and other secondary neurological insults may follow subarachnoid haemorrhage (SAH). Biomarkers have the potential to stratify patient risk and perhaps serve as an early warning sign of delayed ischaemic injury. MethodsSerial cerebrospinal fluid (CSF) samples were collected from 38 consecutive patients with aneurysmal SAH admitted to the neurosurgical intensive care unit. We measured heart-fatty acid-binding protein (H-FABP) and tau protein (τ) levels in the CSF to evaluate their association with brain damage, and their potential as predictors of the long-term outcome. H-FABP and τ were analysed in relation to acute clinical status, assessed by the World Federation of Neurological Surgeons (WFNS) scale, radiological findings, clinical vasospasm, and 6-month outcome. ResultsH-FABP and τ increased after SAH. H-FABP and τ were higher in patients in poor clinical status on admission (WFNS 4–5) compared with milder patients (WFNS 1–3). Elevated H-FABP and τ levels were also observed in patients with early cerebral ischaemia, defined as a CT scan hypodense lesion visible within the first 3 days after SAH. After the acute phase, H-FABP, and τ showed a delayed increase with the occurrence of clinical vasospasm. Finally, patients with the unfavourable outcome (death, vegetative state, or severe disability) had higher peak levels of both proteins compared with patients with good recovery or moderate disability. ConclusionsH-FABP and τ show promise as biomarkers of brain injury after SAH. They may help to identify the occurrence of vasospasm and predict the long-term outcome.

Comparison of microsurgery and endovascular treatment on clinical outcome following poor-grade subarachnoid hemorrhage

Poor-grade (World Federation of Neurological Surgeons [WFNS] clinical grading scale grades IV and V) subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. However, the correlation between the timing, modality of intervention (clipping or coiling) and the clinical outcome is not clear. This study aims to examine this correlation. Patients presenting with WFNS grades IV and V aneurysmal SAH between 1997 and 2008 to a single centre were studied. An aggressive policy of early intervention was followed, and the selection of endovascular versus microsurgical intervention was made according to angiographic rather than clinical features. Clinical outcomes were graded using the modified Rankin scale (mRS) at 6month follow-up. One hundred and forty-three poor-grade patients (23.9% of all 598 aneurysmal SAH patients) were studied. Treatment was microsurgical in 83 (58.0%) and endovascular in 60 (42%) patients. Twenty patients (14.0%) were lost to follow-up. Good outcome (mRS 0-2) at 6months was found in 45 microsurgical patients (63.3%) and 24 endovascular patients (46.1%). This trend towards better clinical outcomes in the microsurgical group was not statistically significant. With an aggressive early treatment policy more than half of the poor-grade SAH patients demonstrated a good clinical outcome. Microsurgery and endovascular treatment, when selected primarily according to angiographic features, were equally likely to achieve good outcome.

Multicenter Prospective Cohort Study on Volume Management After Subarachnoid Hemorrhage

Systemic circulation management has not been established for patients with poor grade aneurysmal subarachnoid hemorrhage (SAH) or delayed cerebral ischemia (DCI) after SAH. The aims of the study were to examine hemodynamic variables in these patients and to establish treatment strategies. A multicenter prospective cohort study of hemodynamic variables from days 1 to 14 was performed using a transpulmonary thermodilution system (PiCCO Plus). Parameters were analyzed by Mann-Whitney test. Multivariate analysis was performed to identify parameters involved in onset of DCI. The subjects were 204 patients, including 138 with poor grade SAH (World Federation of Neurological Surgeons grades IV and V) and 52 who developed DCI. The extravascular lung water index, pulmonary vascular permeability index, and systemic vascular resistance index were significantly greater in patients with poor grade SAH compared with those with good grade SAH (World Federation of Neurological Surgeons I-III) on day 2 (P=0.049, P=0.039, and P=0.038). Cardiac index was significantly lower in patients with poor grade SAH on days 1 and 2 (P=0.027 and P=0.011). In patients with DCI, the global end-diastolic volume index was significantly lower than in those without DCI on days 3 to 5 (P=0.0053; P=0.048; and P=0.048). In multivariate analysis, median global end-diastolic volume index, cardiac index, and systemic vascular resistance index at an early stage of SAH (days 3-6) were independently related to onset of DCI (P=0.023, P=0.013, and P=0.003). Patients with poor grade SAH developed heart failure-like afterload mismatch at an early stage, and those with DCI had decreased global end-diastolic volume index (hypovolemia) in the early stage of SAH. http://www.clinicaltrials.gov. Unique identifier: UMIN000003794.

Copeptin as a Marker for Severity and Prognosis of Aneurysmal Subarachnoid Hemorrhage

BackgroundGrading of patients with aneurysmal subarachnoid hemorrhage (aSAH) is often confounded by seizure, hydrocephalus or sedation and the prediction of prognosis remains difficult. Recently, copeptin has been identified as a serum marker for outcomes in acute ischemic stroke and intracerebral hemorrhage (ICH). We investigated whether copeptin might serve as a marker for severity and prognosis in aSAH.MethodsEighteen consecutive patients with aSAH had plasma copeptin levels measured with a validated chemiluminescence sandwich immunoassay. The primary endpoint was the association of copeptin levels at admission with the World Federation of Neurological Surgeons (WFNS) grade score after resuscitation. Levels of copeptin were compared across clinical and radiological scores as well as between patients with ICH, intraventricular hemorrhage, hydrocephalus, vasospasm and ischemia.ResultsCopeptin levels were significantly associated with the severity of aSAH measured by WFNS grade (P = 0.006), the amount of subarachnoid blood (P = 0.03) and the occurrence of ICH (P = 0.02). There was also a trend between copeptin levels and functional clinical outcome at 6-months (P = 0.054). No other clinical outcomes showed any statistically significant association.ConclusionsCopeptin may indicate clinical severity of the initial bleeding and may therefore help in guiding treatment decisions in the setting of aSAH. These initial results show that copeptin might also have prognostic value for clinical outcome in aSAH.

Anatomical and clinical aspects of cerebral arteriovenous malformations

This article describes the anatomical and clinical aspects of cerebral arteriovenous malformations which from the start won the role of an important cause of death or severe morbidity in the long term due to intracranial hemorrhage and secondary epilepsy. It is the second leading cause of aneurysms after subarachnoid hemorrhage. Cerebral arteriovenous malformations present a nidus fed by one or more nourishing arteries (“feeders”) with deep or superficial venous drainage. Symptoms are determined by the presence of seizures and intraparenchimatous and/ or subarachnoid bleeding. Progressive neurological deterioration can exist, which is attributed to ischemic disorders due to “vascular theft “. Also, it is described the grading system of arteriovenous malformations depending on size, eloquence and venous drainage by Spetzler-Martin system. Also described, a number of other scales with prognostic role and evaluation of the patient’s consciousness, but in was in 1988 when the World Federation of Neurological Surgeons proposed a simplified scale, based on clinical findings of Hunt and Hess scale, translated into GCS, WFNS grading scale SAH.

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Introduction: The World Federation of Neurological Surgeons (WFNS) Scale and Hunt & Hess Grade rely only on clinical presentation to predict mortality following aneurysmal subarachnoid hemorrhage (aSAH). The proposed SAH score incorporates a combination of admission factors that impact mortality following aSAH. Hypothesis: We hypothesize that SAH score improves accuracy of mortality prediction in comparison to WFNS scale and Hunt & Hess Grade. Methods: Prospectively collected data of aSAH patients admitted to our institution between 1991-2009 were reviewed. We analyzed factors that impacted in-hospital SAH mortality following multiple logistic regression analysis. Scores were ‘weighted’ based on relative risk of mortality following stratification of each of these variables. GCS was subdivided into subgroups of 3-4, 5-8, 9-13 and 14-15; age was also split into 4 subgroups: 18-49, 50-69, 70-79 and >80. Medical co-morbidities were subdivided into none, 1 or >/=2 based on co-morbidities derived either from Charlson index or other factors (hypertension, cocaine) known to impact SAH outcomes, only if they were associated with increased mortality on univariate analysis. Results: 1134 patients were included; all-cause SAH hospital mortality was 18.3%. Admission GCS, age and medical co-morbidities significantly impacted mortality following multivariate analysis (P< 0.05). Association with mortality based on GCS was 7%(14-15; score 0), 18%(9-13; score 1), 40%(5-8; score 2) and 65%(3-4; score 4). Mortality based on age was 13%(18-49; score 0), 18%(50-69; score 1), 34% (70-79; score 2) and 46% (>80; score 3). Relationship of co-morbidities and mortality was 9%(none; score 0), 17%(one; score 1) and 32%(two/more; score 2). Summated Scores ranged from 0-8 with increasing mortality at higher scores (0=2%/ 1=6%/ 2=8%/ 3=13%/ 4=30%/ 5=54%/ 6=80%/ 7=89%/ 8=100%). PPV for scores in the range 7-8 was 90%; 6-8 was 84%. NPV for range 0-2 was 94% and 0-3 was 91%. AUC for SAH score was 0.822 (good accuracy), which was superior to WFNS (AUC 0.777, fair accuracy) and Hunt & Hess Grade (AUC 0.771, fair accuracy). Conclusions: The SAH score is a more accurate model than the WFNS scale and Hunt & Hess Grade in predicting mortality following SAH.

Relationship between plasma high mobility group box-1 protein levels and clinical outcomes of aneurysmal subarachnoid hemorrhage

BackgroundHigh-mobility group box 1 (HMGB1), originally described as a nuclear protein that binds to and modifies DNA, is now regarded as a central mediator of inflammation by acting as a cytokine. However, the association of HMGB1 in the peripheral blood with disease outcome and cerebrovasospasm has not been examined in patients with aneurysmal subarachnoid hemorrhage.MethodsIn this study, 303 consecutive patients were included. Upon admission, plasma HMGB1 levels were measured by ELISA. The end points were mortality after 1 year, in-hospital mortality, cerebrovasospasm and poor functional outcome (Glasgow Outcome Scale score of 1 to 3) after 1 year.ResultsUpon admission, the plasma HMGB1 level in patients was statistically significantly higher than that in healthy controls. A multivariate analysis showed that the plasma HMGB1 level was an independent predictor of poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm. A receiver operating characteristic curve showed that plasma HMGB1 level on admission statistically significantly predicted poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm of patients. The area under the curve of the HMGB1 concentration was similar to those of World Federation of Neurological Surgeons (WFNS) score and modified Fisher score for the prediction of poor functional outcome and mortality after 1 year, and in-hospital mortality, but not for the prediction of cerebrovasospasm. In a combined logistic-regression model, HMGB1 improved the area under the curve of WFNS score and modified Fisher score for the prediction of poor functional outcome after 1 year, but not for the prediction of mortality after 1 year, in-hospital mortality, or cerebrovasospasm.ConclusionsHMGB1 level is a useful, complementary tool to predict functional outcome and mortality after aneurysmal subarachnoid hemorrhage. However, HMGB1 determination does not add to the accuracy of prediction of the clinical outcomes.

Local Thrombus Formation at the Coil–Parent Artery Interface during Endovascular Coil Embolization of Cerebral Aneurysms

Fresh thrombus formation at the coil-parent artery interface around the neck of aneurysms is sometimes observed during coil embolization of cerebral aneurysms. We retrospectively analyzed the factors associated with local acute thrombus formation from the data of patients treated over a period of 5 years at our institute. Between November 2004 and March 2009, 242 patients harboring 250 aneurysms were treated with endovascular coil embolization at our institute. The patients were divided into two groups: Group A included 107 patients who were treated and followed up during the initial 29 months of the study, and group B included 135 patients who were treated and followed up during the later 24 months of the study. Clinical and angiographic variables of the procedures were statistically tested for correlation with thrombus formation in the parent arteries. Fresh thrombus formation occurred in six patients with unruptured aneurysms (15%) and 11 patients with ruptured aneurysms (14%) in group A. Among the patients with unruptured aneurysms, the dome-to-neck ratio and location of the aneurysms were independently associated with the risk of thrombus formation, whereas among patients with ruptured aneurysms, a higher World Federation of Neurological Surgeons (WFNS) grade and longer interventional duration were significantly associated with thrombus formation. However, fresh thrombus formation occurred in only two patients with unruptured aneurysms (2.9%) and three patients with ruptured aneurysms (4.4%) in group B. There were no factors that were significantly associated with thrombus formation in all Group B patients. With regard to coil embolization treatment, anatomical and morphological factors seem to be related to intraprocedural thrombus formation in patients with unruptured aneurysms, whereas duration of the intervention and preoperative status are associated factors in patients with ruptured aneurysms. Careful comparison of the thrombus with control angiograms is important to prevent thrombembolic complications. Moreover, the rate of fresh thrombus formation during coil embolization has decreased over the past 5 years at our institute, suggesting the possibility of lowering the incidence of these complications by early detection and treatment.

Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage

Objectives: The pathogenesis of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) is multi-factorial and not completely elucidated. Matrix metalloproteinase-9 (MMP-9) might participate in wall remodeling leading to luminal narrowing. The authors investigated MMP-9 concentration in brain extracellular fluid of aSAH patients and assessed whether this enzyme could have a predictive value for the risk of DCI.Methods: Patients were classified according to the grading of the World Federation of Neurological Surgeons (WFNS) in low- and high-grade patients (WFNS = 1–3, n = 9 and WFNS = 4–5, n = 12, respectively). Cerebral microdialysis probes were placed in brain parenchyma of the respective vascular territory of the aneurysm in 21 consecutive aSAH patients, enrolled in a prospective study on inflammation. Microdialysis samples, collected daily from day 0 until day 8 after aSAH, were retrospectively analyzed for MMP-9 by zymography.Results: Initial concentration of the MMP-9 proform (pro-MMP-9) was significantly higher in high-grade patients as compared to low-grade patients. Furthermore, initial pro-MMP-9 concentration in patients with DCI was seven-fold higher than in asymptomatic patients. Pro-MMP-9 values greater than or equal to 0·27 pg/μl showed 83% sensitivity and 63% specificity in predicting vasospasm. The mature form of the MMP-9 could be preferentially detected in patients with DCI but was usually low.Discussion: The pro and mature forms of MMP-9 were released locally in the brain after aSAH. Pro-MMP-9 release was related to WFNS grade severity. This protease, considered as playing a critical role in endothelial basal membrane damage, may contribute to the inflammatory processes leading to arterial narrowing.

Intraoperative mild hypothermia for postoperative neurological deficits in intracranial aneurysm patients.

Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage, which is one of the most devastating clinical conditions. Clinically, it can be classified into five grades using the Hunt-Hess or World Federation of Neurological Surgeons (WFNS) scale. Grades 4 and 5 predict poor prognosis and are called 'poor grade', while grade 1, 2, and 3 are known as 'good grade'. Disturbances of intracranial homeostasis and brain metabolism are known to play certain roles in the sequelae. Hypothermia has a long history of being used to reduce metabolism rate, thereby protecting organs in cases where metabolism is disturbed and potentially harmful. To assess the effect of intraoperative mild hypothermia on postoperative death and neurological deficits in patients with intracranial aneurysms (ruptured or unruptured). We searched the Cochrane Stroke Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1950 to September 2011), EMBASE (1980 to September 2011), Science Citation Index (1900 to September 2011) and 11 Chinese databases (September 2011). We also searched ongoing trials registers (September 2011) and scanned reference lists of retrieved records. We included only randomised controlled trials comparing intraoperative mild hypothermia (32°C to 35°C) with control (no hypothermia) in patients with intracranial aneurysms (ruptured or unruptured). Two review authors independently selected trials and assessed the risk of bias for each included study. We presented data as risk ratio (RR) with 95% confidence intervals (CI). We included three studies enrolling 1158 patients. Each study observed an increased rate of good recovery with intraoperative mild hypothermia, but the effect sizes were not sufficient for statistical significance. A total of 76 of 577 patients (13.1%) who received hypothermia and 93 of 581 patients (16.0%) who did not receive hypothermia were dead or dependent. A total of 1086 of the1158 patients (93.8%) had good-grade aneurysmal subarachnoid haemorrhage. A random-effects meta-analysis resulted in a summarised RR of 0.82 (95% CI 0.62 to 1.09, P value 0.17). In patients with poor-grade aneurysmal subarachnoid haemorrhage, one of seven in the hypothermia group and one of six in the control group were dead or dependent (RR 0.86, 95% CI 0.07 to 10.96, P value 0.91). In patients without subarachnoid haemorrhage, three of 30 patients (10%) in the hypothermia group, and four of 29 patients (13.8%) in the control group were dead or dependent (RR 0.72, 95% CI 0.18 to 2.96, P value 0.65). In patients with good-grade aneurysmal subarachnoid haemorrhage, intraoperative mild hypothermia might prevent death or dependency in activities of daily living for a few of them. However, the confidence intervals include the possibility of both benefit and harm. There is no evidence that intraoperative mild hypothermia is harmful. This treatment should not be routinely applied. In patients with poor-grade aneurysmal subarachnoid haemorrhage or without subarachnoid haemorrhage, there are insufficient data to draw any conclusions. A high-quality randomised clinical trial of intraoperative mild hypothermia for postoperative neurological deficits in patients with poor-grade aneurysmal subarachnoid haemorrhage might be feasible.