High-flow bypass using saphenous vein grafts with trapping of ruptured blood blister-like aneurysms of the internal carotid artery: patient series.

BACKGROUND: Trapping an aneurysm after the establishment of an extracranial to intracranial high-flow bypass is considered the optimal surgical strategy for ruptured blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA). For high-flow bypass surgeries, a radial artery graft is generally preferred over a saphenous vein graft (SVG). However, SVGs can be advantageous in acute-phase surgeries because of their greater length, easy manipulability, ability to act as high-flow conduits, and reduced risk of vasospasms. In this study, the authors presented five cases of ruptured BBAs treated with high-flow bypass using an SVG followed by BBA trapping, and they reported on surgical outcomes and operative nuances that may help avoid potential pitfalls. OBSERVATIONS: After the surgeries, there were no ischemic or hemorrhagic complications, including symptomatic vasospasms. In three of the five cases, postoperative modified Rankin scale scores were between 0 and 2 at the 3-month follow-up. In one case, the SVG spontaneously occluded after surgery while the protective superficial temporal artery (STA) to middle cerebral artery (MCA) bypass became dominant, and the patient experienced no ischemic symptoms. LESSONS: High-flow bypass using an SVG with a protective STA-MCA bypass followed by BBA trapping is a safe and effective treatment strategy.

Neurosurgical education in Egypt and Africa.

OBJECTIVE: Africa still significantly lags in the development of neurosurgery. Egypt, located in North Africa, is well-developed in this specialty, with the largest number of neurosurgeons among all African countries. This article provides insight into neurosurgical training in Egypt, the challenges African neurosurgeons are facing, and the requirements needed to enhance neurosurgical education and build up the required neurosurgical capacity in Africa. METHODS: The information presented in the current work was collected from databases of the Egyptian Society of Neurological Surgeons and the World Federation of Neurosurgical Societies. RESULTS: There are two types of neurosurgical certification in Egypt. The first type is granted by the universities (MD), and the second is awarded by the Ministry of Health (Fellow of Neurosurgery). The program in both types ranges from 6 to 9 years. The number of qualified neurosurgeons in Egypt constitutes one-third of the total number of African neurosurgeons. There is a significant shortage of neurological surgeons in Africa, and the distribution is entirely unbalanced, with the majority of neurosurgeons concentrated in the North and South regions. The most important challenge facing neurosurgery in Africa is lack of resources, which is considered to be the main obstacle to the development of neurosurgery. Other challenges include the limited number of neurosurgeons, lack of training programs, and lack of collaboration among the different regions. CONCLUSIONS: Proper collaboration among the different regions within the African continent regarding neurosurgical education will enhance African neurosurgical capacity and make neurosurgery an independent specialty. The definite functional polarity among different regions, regarding both the number of qualified neurosurgeons and the neurosurgical capacity, is an important factor that could help in the development of neurosurgery in this continent.

An analysis of cross-continental scholarship requirements during neurosurgical training and national research productivity.

OBJECTIVE: Engagement in research and scholarship is considered a hallmark of neurosurgical training. However, the participation of neurosurgical trainees in this experience has only recently been analyzed and described in the United States, with little, if any, data available regarding the research environment in neurosurgical training programs across the globe. Here, the authors set out to identify requirements for research involvement and to quantify publication rates in leading neurosurgical journals throughout various nations across the globe. METHODS: The first aim was to identify the research requirements set by relevant program-accrediting and/or board-certifying agencies via query of the literature and published guidelines. For the second part of the study, the authors attempted to determine each country's neurosurgical research productivity by quantifying publications in the various large international neurosurgical journals-World Neurosurgery, Journal of Neurosurgery, and Neurosurgery-via a structured search of PubMed. RESULTS: Data on neurosurgical training requirements addressing research were available for 54 (28.1%) of 192 countries. Specific research requirements were identified for 39 countries, partial requirements for 8, and no requirements for 7. Surprisingly, the authors observed a trend of increased average research productivity with the absence of designated research requirements, although this finding is not unprecedented in the literature. CONCLUSIONS: A variety of countries of various sizes and neurosurgical workforce densities across the globe have instituted research requirements during training and/or prior to board certification in neurosurgery. These requirements range in intensity from 1 publication or presentation to the completion of a thesis or dissertation and occur at various time points throughout training. While these requirements do not correlate directly to national research productivity, they may provide a foundation for developing countries to establish a culture of excellence in research.

The impact of African-trained neurosurgeons on sub-Saharan Africa.

OBJECTIVE: Sub-Saharan Africa (SSA) represents 17% of the world's land, 14% of the population, and 1% of the gross domestic product. Previous reports have indicated that 81/500 African neurosurgeons (16.2%) worked in SSA-i.e., 1 neurosurgeon per 6 million inhabitants. Over the past decades, efforts have been made to improve neurosurgery availability in SSA. In this study, the authors provide an update by means of the polling of neurosurgeons who trained in North Africa and went back to practice in SSA. METHODS: Neurosurgeons who had full training at the World Federation of Neurosurgical Societies (WFNS) Rabat Training Center (RTC) over the past 16 years were polled with an 18-question survey focused on demographics, practice/case types, and operating room equipment availability. RESULTS: Data collected from all 21 (100%) WFNS RTC graduates showed that all neurosurgeons returned to work to SSA in 12 different countries, 90% working in low-income and 10% in lower-middle-income countries, defined by the World Bank as a Gross National Income per capita of ≤ US$995 and US$996-$3895, respectively. The cumulative population in the geographical areas in which they practice is 267 million, with a total of 102 neurosurgeons reported, resulting in 1 neurosurgeon per 2.62 million inhabitants. Upon return to SSA, WFNS RTC graduates were employed in public/private hospitals (62%), military hospitals (14.3%), academic centers (14.3%), and private practice (9.5%). The majority reported an even split between spine and cranial and between trauma and elective; 71% performed between 50 and more than 100 neurosurgical procedures/year. Equipment available varied across the cohort. A CT scanner was available to 86%, MRI to 38%, surgical microscope to 33%, endoscope to 19.1%, and neuronavigation to 0%. Three (14.3%) neurosurgeons had access to none of the above. CONCLUSIONS: Neurosurgery availability in SSA has significantly improved over the past decade thanks to the dedication of senior African neurosurgeons, organizations, and volunteers who believed in forming the new neurosurgery generation in the same continent where they practice. Challenges include limited resources and the need to continue expanding efforts in local neurosurgery training and continuing medical education. Focus on affordable and low-maintenance technology is needed.

Patterns of care for ruptured aneurysms of the middle cerebral artery: analysis of a Swiss national database (Swiss SOS).

OBJECTIVE: The objective of this study was to determine patterns of care and outcomes in ruptured intracranial aneurysms (IAs) of the middle cerebral artery (MCA) in a contemporary national cohort. METHODS: The authors conducted a retrospective analysis of prospective data from a nationwide multicenter registry of all aneurysmal subarachnoid hemorrhage (aSAH) cases admitted to a tertiary care neurosurgical department in Switzerland in the years 2009-2015 (Swiss Study on Aneurysmal Subarachnoid Hemorrhage [Swiss SOS]). Patterns of care and outcomes at discharge and the 1-year follow-up in MCA aneurysm (MCAA) patients were analyzed and compared with those in a control group of patients with IAs in locations other than the MCA (non-MCAA patients). Independent predictors of a favorable outcome (modified Rankin Scale score ≤ 3) were identified, and their effect size was determined. RESULTS: Among 1866 consecutive aSAH patients, 413 (22.1%) harbored an MCAA. These MCAA patients presented with higher World Federation of Neurosurgical Societies grades (p = 0.007), showed a higher rate of concomitant intracerebral hemorrhage (ICH; 41.9% vs 16.7%, p < 0.001), and experienced delayed cerebral ischemia (DCI) more frequently (38.9% vs 29.4%, p = 0.001) than non-MCAA patients. After adjustment for confounders, patients with MCAA were as likely as non-MCAA patients to experience DCI (aOR 1.04, 95% CI 0.74-1.45, p = 0.830). Surgical treatment was the dominant treatment modality in MCAA patients and at a significantly higher rate than in non-MCAA patients (81.7% vs 36.7%, p < 0.001). An MCAA location was a strong independent predictor of surgical treatment (aOR 8.49, 95% CI 5.89-12.25, p < 0.001), despite statistical adjustment for variables traditionally associated with surgical treatment, such as (space-occupying) ICH (aOR 1.73, 95% CI 1.23-2.45, p = 0.002). Even though MCAA patients were less likely to die during the acute hospitalization (aOR 0.52, 0.30-0.91, p = 0.022), their rate of a favorable outcome was lower at discharge than that in non-MCAA patients (55.7% vs 63.7%, p = 0.003). At the 1-year follow-up, 68.5% and 69.6% of MCAA and non-MCAA patients, respectively, had a favorable outcome (p = 0.676). CONCLUSIONS: Microsurgical occlusion remains the predominant treatment choice for about 80% of ruptured MCAAs in a European industrialized country. Although patients with MCAAs presented with worse admission grades and greater rates of concomitant ICH, in-hospital mortality was lower and long-term disability was comparable to those in patients with non-MCAA.

Clip-first policy versus coil-first policy for the exclusion of middle cerebral artery aneurysms.

OBJECTIVE: Middle cerebral artery (MCA) aneurysms are a particular subset of intracranial aneurysms that can be excluded by clipping or coiling. A comparison of the results between these two methods is often limited by a selection bias in which wide-neck and large aneurysms are frequently treated with surgery. Here, the authors report the results of two centers using opposing policies in the management of MCA aneurysms: one center used a clip-first policy while the other used a coil-first policy, which limited the selection bias and ensured a good comparison of these two treatment modalities. METHODS: All patients treated for either ruptured or unruptured MCA aneurysms at one of two institutions between January 2012 and December 2015 were eligible for inclusion in this study. At one center a clip-first policy was applied, whereas the other applied a coil-first policy. The authors retrospectively reviewed the medical records of these patients and compared their clinical and radiological outcomes. RESULTS: A total of 187 aneurysms were treated during the inclusion period; 88 aneurysms were treated by coiling and 99 aneurysms by clipping. The baseline patient and radiological characteristics were similar between the two groups, but the clinical presentation of the ruptured aneurysm cohort differed slightly. In the ruptured cohort (n = 90), although patients in the coiling group had a higher rate of additional surgery, the complication rate, functional outcome, and risk of death were similar between the two treatment groups. In the unruptured cohort (n = 97), the complication rate, functional outcome, and risk of death were also similar between the two treatment groups, although the risk of discomfort related to the temporal muscle atrophy was higher in the surgical group. Overall, the rate of complete occlusion was higher in the clipping group (84.2%) than in the coiling group (31%), which led to a higher risk in the coiling group of aneurysm retreatment within the first 2 years (p = 0.04). CONCLUSIONS: Clipping and coiling for MCA aneurysm treatment provide the same clinical outcome for ruptured and unruptured aneurysms. However, clipping provides higher short- and long-term rates of complete exclusion, which in turn decreases the risk of aneurysm retreatment. Whether this lower occlusion rate can have a clinical impact in the long-term must be further evaluated.

Global neurosurgery: innovators, strategies, and the way forward.

Around the world today, low- and middle-income countries (LMICs) have not benefited from advancements in neurosurgery; most have minimal or even no neurosurgical capacity in their entire country. In this paper, the authors examine in broad strokes the different ways in which individuals, organizations, and universities engage in global neurosurgery to address the global challenges faced in many LMICs. Key strategies include surgical camps, educational programs, training programs, health system strengthening projects, health policy changes/development, and advocacy. Global neurosurgery has begun coalescing with large strides taken to develop a coherent voice for this work. This large-scale collaboration via multilateral, multinational engagement is the only true solution to the issues we face in global neurosurgery. Key players have begun to come together toward this ultimate solution, and the future of global neurosurgery is bright.

Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: In patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration. METHODS: In this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures. RESULTS: Twenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119). CONCLUSIONS: Preliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

Impact of perioperative aneurysm rebleeding after subarachnoid hemorrhage.

OBJECTIVE: Aneurysm rebleeding is a major cause of death and morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). Recognizing the predictors of rebleeding might help to identify patients who will benefit from acute management. This study was performed to investigate the predictors of aneurysm rebleeding and their impact on clinical outcomes in the preoperative, intraoperative, and postoperative periods. METHODS: The incidence of rebleeding, demographic data, and clinical data from 4933 patients with aneurysmal SAH beginning in the year 2000 were retrospectively analyzed in the Nagasaki SAH Registry Study. The authors performed multiple logistic regression analyses to identify the risk factors contributing to rebleeding and outcome after SAH. RESULTS: Preoperative rebleeding occurred in 7.2% of patients. Patient age (p = 0.01), multiple aneurysms (p < 0.01), aneurysm size (p < 0.0001), and heart disease (p = 0.03) were significantly associated with preoperative rebleeding. Conversely, intraoperative rebleeding occurred in 11.2% of patients. Aneurysm location (anterior communicating artery [ACoA]), family history (p = 0.02), preoperative rebleeding (p < 0.01), and clipping/coiling (p < 0.0001) were significantly associated with intraoperative rebleeding. Interaction analysis showed that clipping significantly affected intraoperative rebleeding at the ACoA (OR 4.00; 95% CI 1.82-8.80; p < 0.001). Postoperative rebleeding occurred in 2.4% of patients. Coiling/clipping (p < 0.0001) and intraoperative rebleeding (p < 0.01) were significantly associated with postoperative rebleeding. Rebleeding in all time periods examined significantly contributed to the clinical outcome after SAH. CONCLUSIONS: Aneurysm rebleeding after SAH has specific characteristics in the preoperative, intraoperative, and postoperative periods, and all of these characteristics contribute to the clinical outcome. The ACoA has a higher risk of intraoperative rebleeding, and endovascular coiling could be a good candidate in terms of techniques for preventing intraoperative rebleeding, although complete aneurysm obliteration should be accomplished.

Decrease of blood flow velocity in the middle cerebral artery after stellate ganglion block following aneurysmal subarachnoid hemorrhage: a potential vasospasm treatment?

OBJECTIVE: Cerebral vasospasm (CV) is a delayed, sustained contraction of the cerebral arteries that tends to occur 3-14 days after aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured aneurysm. Vasospasm potentially leads to delayed cerebral ischemia, and despite medical treatment, 1 of 3 patients suffer a persistent neurological deficit. Bedside transcranial Doppler (TCD) ultrasonography is used to indirectly detect CV through recognition of an increase in cerebral blood flow velocity (CBFV). The present study aimed to use TCD ultrasonography to monitor how CBFV changes on both the ipsi- and contralateral sides of the brain in the first 24 hours after patients have received a stellate ganglion block (SGB) to treat CV that persists despite maximum standard therapy. METHODS: The data were culled from records of patients treated between 2013 and 2017. Patients were included if an SGB was administered following aSAH, whose CBFV was ≥ 120 cm/sec and who had either a focal neurological deficit or reduced consciousness despite having received medical treatment and blood pressure management. The SGB was performed on the side where the highest CBFV had been recorded with 8-10 ml ropivacaine 0.2%. The patient's CBFV was reassessed after 2 and 24 hours. RESULTS: Thirty-seven patients (male/female ratio 18:19), age 17-70 years (mean age 49.9 ± 11.1), who harbored 13 clipped and 22 coiled aneurysms (1 patient received both a coil and a clip, and 3 patients had 3 untreated aneurysms) had at least one SGB. Patients received up to 4 SGBs, and thus the study comprised a total of 76 SGBs.After the first SGB, CBFV decreased in 80.5% of patients after 2 hours, from a mean of 160.3 ± 28.2 cm/sec to 127.5 ± 34.3 cm/sec (p < 0.001), and it further decreased in 63.4% after 24 hours to 137.2 ± 38.2 cm/sec (p = 0.007). A similar significant effect was found for the subsequent SGB. Adding clonidine showed no significant effect on either the onset or the duration of the SGB. Contralateral middle cerebral artery (MCA) blood flow was not reduced by the SGB. CONCLUSIONS: To the authors' knowledge, this is the largest study on the effects of administering an SGB to aSAH patients after aneurysm rupture. The data showed a significant reduction in ipsilateral CBFV (MCA 20.5%) after SGB, lasting in about two-thirds of cases for over 24 hours with no major complications resulting from the SGB.

Between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository.

OBJECTIVE: Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country differences were quantified with the median odds ratio (MOR), which can be interpreted as the ratio of odds of unfavorable outcome between a typical high-risk and a typical low-risk center or country. RESULTS: The proportion of patients with unfavorable outcome was 27% (n = 1599). The authors found substantial between-center differences (MOR 1.26, 95% CI 1.16-1.52), which could not be explained by patient characteristics and timing of aneurysm treatment (adjusted MOR 1.21, 95% CI 1.11-1.44). They observed no between-country differences (adjusted MOR 1.13, 95% CI 1.00-1.40). CONCLUSIONS: Clinical outcomes after aSAH differ between centers. These differences could not be explained by patient characteristics or timing of aneurysm treatment. Further research is needed to confirm the presence of differences in outcome after aSAH between hospitals in more recent data and to investigate potential causes.

Acute kidney injury after aneurysmal subarachnoid hemorrhage and its effect on patient outcome: an exploratory analysis.

OBJECTIVE: Acute kidney injury (AKI) is associated with death in critically ill patients, but this complication has not been well characterized after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of this study was to determine the incidence of AKI after aSAH and to identify risk factors for renal dysfunction. Secondary objectives were to examine what effect AKI has on patient mortality and functional outcome at 12 weeks post-aSAH. METHODS: The authors performed a post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial data set (clinical trial registration no.: NCT00111085, https://clinicaltrials.gov). The primary outcome of interest was the development of AKI, which was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes of interest were death and a modified Rankin Scale score greater than 2 at 12 weeks post-aSAH. Propensity score matching was used to assess for a significant treatment effect related to clazosentan administration and AKI. Univariate analysis, locally weighted scatterplot smoothing (LOWESS) curves, and stepwise logistic regression models were used to evaluate for associations between baseline or disease-related characteristics and study outcomes. RESULTS: One hundred fifty-six (38%) of the 413 patients enrolled in the CONSCIOUS-1 trial developed AKI during their ICU stay. A history of hypertension (p < 0.001) and the number of nephrotoxic medications administered (p = 0.029) were independent predictors of AKI on multivariate analysis. AKI was an independent predictor of death (p = 0.028) but not a poor functional outcome (p = 0.21) on multivariate testing. Unresolved renal dysfunction was the strongest independent predictor of death in this cohort (p < 0.001). CONCLUSIONS: AKI is a common complication following aSAH. Patients with premorbid hypertension and those treated with nephrotoxic medications may be at greater risk for renal dysfunction. AKI appears to confer an increased probability of death after aSAH.

Rebleeding drives poor outcome in aneurysmal subarachnoid hemorrhage independent of delayed cerebral ischemia: a propensity-score matched cohort study.

OBJECTIVE: Delayed cerebral ischemia (DCI) and aneurysm rebleeding contribute to morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH); however, the relationship between their impacts on overall functional outcome is incompletely understood. METHODS: The authors conducted a cohort study of all aSAH during the study period from 2001 to 2016. Primary end points were overall functional outcome and ischemic aSAH sequelae, defined as delayed cerebral ischemia (DCI), DCI with infarction, symptomatic vasospasm (SV), and global cerebral edema (GCE). Outcomes were compared between the rebleed and nonrebleed cohorts overall and after propensity-score matching (PSM) for risk factors and treatment modality. Univariate and multivariate ordered logistic regression analyses for functional outcomes were performed in the PSM cohort to identify predictors of poor outcome. RESULTS: Four hundred fifty-five aSAH cases admitted within 24 hours of aneurysm rupture were included, of which 411 (90%) experienced initial aneurysm ruptures only, while 44 (10%) had clinically confirmed rebleeding. In the overall cohort, rebleeding was associated with significantly worse functional outcome, longer intensive care unit length of stay (LOS), and GCE (all p < 0.01); treatment modality, overall LOS, DCI, DCI with infarction, and SV were nonsignificant. In the PSM analysis of 43 matched rebleed and 43 matched nonrebleed cases, only poor functional outcome and GCE remained significantly associated with rebleeding (p < 0.01 and p = 0.02, respectively). Multivariate regression identified that both rebleeding (HR 21.5, p < 0.01) and DCI (HR 10.1, p = 0.01) independently predicted poor functional outcome. CONCLUSIONS: Rebleeding and DCI after aSAH are highly morbid and potentially deadly events after aSAH, which appear to have independent negative impacts on overall functional outcome. Early rebleeding did not significantly affect the risk of delayed ischemic complications.

Neutrophil-to-lymphocyte ratio as an independent predictor for unfavorable functional outcome in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Stroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008-2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Patients' radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures. RESULTS: Overall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median [IQR] NLR 5.8 [3.0-10.0] for mRS score 0-2 vs NLR 8.3 [4.5-12.6] for mRS score 3-6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR [95% CI] 1.014 [1.001-1.027]; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden's index = 0.211; mRS score 3-6: 94/153 [61.4%] for NLR ≥ 7.05 vs 67/166 [40.4%] for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score-matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3-6 at 3 months: NLR ≥ 7.05 82/133 [61.7%] vs NLR < 7.05 62/133 [46.6%]; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 [27.8%] vs NLR < 7.05 27/133 [20.3%]; p = 0.131). CONCLUSIONS: Among aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.

Secondary hemorrhagic complications in aneurysmal subarachnoid hemorrhage: when the impact hits hard.

OBJECTIVE: Clinical data on secondary hemorrhagic complications (SHCs) in patients with aneurysmal subarachnoid hemorrhage (SAH) are sparse and mostly limited to ventriculostomy-associated SHCs. This study aimed to elucidate the incidence, risk factors, and impact on outcome of SHCs in a large cohort of SAH patients. METHODS: All consecutive patients with ruptured aneurysms treated between January 2003 and June 2016 were eligible for this study. Patients' charts were reviewed for clinical data, and imaging studies were reviewed for radiographic data. SHCs were divided into those associated with ventriculostomy and those not associated with ventriculostomy, as well as into major and minor bleeding forms, depending on clinical impact. RESULTS: Sixty-two (6.6%) of the 939 patients included in the final analysis developed SHCs. Ventriculostomy-associated bleedings (n = 16) were independently predicted by mono- or dual-antiplatelet therapy after aneurysm treatment (p = 0.028, adjusted odds ratio [aOR] = 10.28; and p = 0.026, aOR = 14.25, respectively) but showed no impact on functional outcome after SAH. Periinterventional use of thrombolytic agents for early effective anticoagulation was the only independent predictor (p = 0.010, aOR = 4.27) of major SHCs (n = 38, 61.3%) in endovascularly treated patients. In turn, a major SHC was independently associated with poor outcome at the 6-month follow-up (modified Rankin Scale score > 3). Blood thinning drug therapy prior to SAH was not associated with SHC risk. CONCLUSIONS: SHCs present a rare sequela of SAH. Antiplatelet therapy during (but not before) SAH increases the risk of ventriculostomy-associated bleedings, but without further impact on the course and outcome of SAH. The use of thrombolytic agents for early effective anticoagulation carries relevant risk for major SHCs and poor outcome.

Assessment of lipoprotein-associated phospholipase A2 level and its changes in the early stages as predictors of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI. METHODS: The authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed. RESULTS: Forty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 µg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 µg/L at D1 and 167.24 ± 54.10 µg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 µg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05-18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18-9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03-18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 µg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 µg/L (p < 0.001). CONCLUSIONS: The serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.

Association between vasoactive peptide urotensin II in plasma and cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a potential therapeutic target.

OBJECTIVECerebral vasospasm (VS) is a severe complication of aneurysmal subarachnoid hemorrhage (SAH). Urotensin II (UII) is a potent vasoactive peptide activating the urotensin (UT) receptor, potentially involved in brain vascular pathologies. The authors hypothesized that UII/UT system antagonism with the UT receptor antagonist/biased ligand urantide may be associated with post-SAH VS. The objectives of this study were 2-fold: 1) to leverage an experimental mouse model of SAH with VS in order to study the effect of urotensinergic system antagonism on neurological outcome, and 2) to investigate the association between plasma UII level and symptomatic VS after SAH in human patients.METHODSA mouse model of SAH was used to study the impacts of UII and the UT receptor antagonist/biased ligand urantide on VS and neurological outcome. Then a clinical study was conducted in the setting of a neurosurgical intensive care unit. Plasma UII levels were measured in SAH patients daily for 9 days, starting on the 1st day of hospitalization, and were compared with plasma UII levels in healthy volunteers.RESULTSIn the mouse model, urantide prevented VS as well as SAH-related fine motor coordination impairment. Seventeen patients with SAH and external ventricular drainage were included in the clinical study. The median plasma UII level was 43 pg/ml (IQR 14-80 pg/ml). There was no significant variation in the daily median plasma UII level (median value for the 17 patients) from day 0 to day 8. The median level of plasma UII during the 9 first days post-SAH was higher in patients with symptomatic VS than in patients without VS (77 pg/ml [IQR 33.5-111.5 pg/ml] vs 37 pg/ml [IQR 21-46 pg/ml], p < 0.05). Concerning daily measures of plasma UII levels in VS, non-VS patients, and healthy volunteers, we found a significant difference between SAH patients with VS (median 66 pg/ml [IQR 30-110 pg/ml]) and SAH patients without VS (27 pg/ml [IQR 15-46 pg/ml], p < 0.001) but no significant difference between VS patients and healthy volunteers (44 pg/ml [IQR 27-51 pg/ml]) or between non-VS patients and healthy volunteers.CONCLUSIONSThe results of this study suggest that UT receptor antagonism with urantide prevents VS and improves neurological outcome after SAH in mice and that an increase in plasma UII is associated with cerebral VS subsequent to SAH in humans. The causality link between circulating UII and VS after SAH remains to be established, but according to our data the UT receptor is a potential therapeutic target in SAH.

Quantitative versus qualitative blood amount assessment as a predictor for shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Reliable tools are lacking to predict shunt-dependent hydrocephalus (SDHC) development after aneurysmal subarachnoid hemorrhage (aSAH). Quantitative volumetric measurement of hemorrhagic blood is a good predictor of SDHC but might be impractical in the clinical setting. Qualitative assessment performed using scales such as the modified Fisher scale (mFisher) and the original Graeb scale (oGraeb) is easier to conduct but provides limited predictive power. In between, the modified Graeb scale (mGraeb) keeps the simplicity of the qualitative scales yet adds assessment of acute hydrocephalus, which might improve SDHC-predicting capabilities. In this study the authors investigated the likely capabilities of the mGraeb and compared them with previously validated methods. This research also aimed to define a tailored mGraeb cutoff point for SDHC prediction. METHODS: The authors performed retrospective analysis of patients admitted to their institution with the diagnosis of aSAH between May 2013 and April 2016. Out of 168 patients, 78 were included for analysis after the application of predefined exclusion criteria. Univariate and multivariate analyses were conducted to evaluate the use of all 4 methods (quantitative volumetric assessment and the mFisher, oGraeb, and mGraeb scales) to predict the likelihood of SDHC development based on clinical data and blood amount assessment on initial CT scans. RESULTS: The mGraeb scale was demonstrated to be the most robust predictor of SDHC, with an area under the curve (AUC) of 0.848 (95% CI 0.763-0.933). According to the AUC results, the performance of the mGraeb scale was significantly better than that of the oGraeb scale (χ2 = 4.49; p = 0.034) and mFisher scale (χ2 = 7.21; p = 0.007). No statistical difference was found between the AUCs of the mGraeb and the quantitative volumetric measurement models (χ2 = 12.76; p = 0.23), but mGraeb proved to be the simplest model since it showed the lowest Akaike information criterion (66.4), the lowest Bayesian information criterion (71.2), and the highest R2Nagelkerke coefficient (39.7%). The initial mGraeb showed more than 85% specificity for predicting the development of SDHC in patients presenting with a score of 12 or more points. CONCLUSIONS: According to the authors' data, the mGraeb scale is the simplest model that correlates well with SDHC development. Due to limited scientific evidence of treatments aimed at SDHC prevention, we propose an mGraeb score higher than 12 to identify patients at risk with high specificity. This mGraeb cutoff point might also serve as a useful prognostic tool since patients with SDHC after aSAH have worse functional outcomes.

Aneurysm rebleeding before therapy: a predictable disaster?

OBJECTIVECurrent guidelines for subarachnoid hemorrhage (SAH) include early aneurysm treatment within 72 hours after ictus. However, aneurysm rebleeding remains a crucial complication of SAH. The aim of this study was to identify independent predictors allowing early stratification of SAH patients for rebleeding risk.METHODSAll patients admitted to the authors' institution with ruptured aneurysms during a 14-year period were eligible for this retrospective study. Demographic and radiographic parameters, aneurysm characteristics, medical history, and medications as well as baseline parameters at admission (blood pressure and laboratory parameters) were evaluated in univariate and multivariate analyses. A novel risk score was created using independent risk factors.RESULTSData from 984 cases could be included into the final analysis. Aneurysm rebleeding occurred in 58 cases (5.9%), and in 48 of these cases (82.8%) rerupture occurred within 24 hours after SAH. Of over 30 tested associations, preexisting arterial hypertension (p = 0.02; adjusted odds ratio [aOR] 2.56, 1 score point), aneurysm location at the basilar artery (p = 0.001, aOR 4.5, 2 score points), sac size ≥ 9 mm (p = 0.04, aOR 1.9, 1 score point), presence of intracerebral hemorrhage (p = 0.001, aOR 4.29, 2 score points), and acute hydrocephalus (p < 0.001, aOR 6.27, 3 score points) independently predicted aneurysm rebleeding. A score built upon these parameters (0-9 points) showed a good diagnostic accuracy (p < 0.001, area under the curve 0.780) for rebleeding prediction.CONCLUSIONSCertain patient-, aneurysm-, and SAH-specific parameters can reliably predict aneurysm rerupture. A score developed according to these parameters might help to identify individuals that would profit from immediate aneurysm occlusion.

Global neurosurgery: current and potential impact of neurosurgeons at the World Health Organization and the World Health Assembly. Executive summary of the World Federation of Neurosurgical Societies-World Health Organization Liaison Committee at the 71st World Health Assembly.

Since the creation of the World Health Organization (WHO) in 1948, the annual World Health Assembly (WHA) has been the major forum for discussion, debate, and approval of the global health agenda. As such, it informs the framework for the policies and budgets of many of its Member States. For most of its history, a significant portion of the attention of health ministers and Member States has been given to issues of clean water, vaccination, and communicable diseases. For neurosurgeons, the adoption of WHA Resolution 68.15 changed the global health landscape because the importance of surgical care for universal health coverage was highlighted in the document. This resolution was adopted in 2015, shortly after the publication of The Lancet Commission on Global Surgery Report titled "Global Surgery 2030: evidence and solutions for achieving health, welfare and economic development." Mandating global strengthening of emergency and essential surgical care and anesthesia, this resolution has led to the formation of surgical and anesthesia collaborations that center on WHO and can be facilitated via the WHA. Participation by neurosurgeons has grown dramatically, in part due to the official relations between WHO and the World Federation of Neurosurgical Societies, with the result that global neurosurgery is gaining momentum.