Course Of Subarachnoid Hemorrhage Research Articles

Morphometric Study of the Initial Ventricular Indices to Predict the Complications and Outcome of Aneurysmal Subarachnoid Hemorrhage

Acute hydrocephalus is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Several ventricular indices have been introduced to enable measurements of ventricular morphology. Previously, researchers have showed their diagnostic value for various neurological disorders. In this study, we evaluated the association between ventricular indices and the clinical course, occurrence of complications and outcome of SAH. A total of 745 SAH patients with available early admission computed tomography scans were included in the analyses. Six ventricular indices (bifrontal, bicaudate, ventricular and third ventricle ratios and Evans' and Huckman's indices) were measured. Primary endpoints included the occurrence of cerebral infarctions, in-hospital mortality and a poor outcome at 6 months. Secondary endpoints included different adverse events in the course of SAH. Clinically relevant cut-offs for the indices were determined using receiver operating curves. Univariate analyses were performed. Multivariate analyses were conducted on significant findings in a stepwise backward regression model. The higher the values of the ventricular indices were and the older the patient was, the higher the WFNS and Fisher's scores were, and the lower the SEBES score was at admission. Patients with larger ventricles showed a shorter duration of intracranial pressure increase > 20 mmHg and required decompressive craniectomy less frequently. Ventricular indices were independently associated with the parameters of inflammatory response after SAH (C-reactive protein in serum and interleukin-6 in cerebrospinal fluid and fever). Finally, there were independent correlations between larger ventricles and all the primary endpoints. The lower risk of intracranial pressure increase and absence of an association with vasospasm or systemic infections during SAH, and the poorer outcome in individuals with larger ventricles might be related to a more pronounced neuroinflammatory response after aneurysmal bleeding. These observations might be helpful in the development of specific medical and surgical treatment strategies for SAH patients depending on the initial ventricle measurements.

Aneurysm Location Affects Clinical Course and Mortality in Patients With Subarachnoid Hemorrhage.

ObjectiveThe influence of preexisting factors on the clinical course of patients with subarachnoid hemorrhage (SAH), such as patient age, arterial hypertension, and aneurysm characteristics, is still a matter of debate. However, the specific impact of the exact aneurysm location has not received adequate attention. Therefore, the aim of this study was to investigate the influence of aneurysm location as a preexisting factor on the clinical course and mortality.MethodsThe data of consecutive patients with aneurysmal SAH who were treated from October 2010 to July 2020 were retrospectively analyzed. We distinguished four aneurysm locations: the anterior complex, internal carotid artery (ICA), middle cerebral artery (MCA), and posterior circulation. Logistic regression analysis and receiver operating characteristics were used to investigate the influence of aneurysm location on the occurrence of acute hydrocephalus, Delayed Cerebral Ischemia (DCI), neurological outcome, and in-hospital mortality. Neurological outcome was assessed 3 months after discharge using the Glasgow Outcome Scale.ResultsA total of 603 patients were included in this study. Patients with MCA aneurysms were 2.52 times less likely to develop acute hydrocephalus compared to patients with anterior complex aneurysms (p = 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm and least frequently in MCA aneurysms (p = 0.014). In ICA aneurysms, mortality was 2.56-fold higher than in patients with aneurysms of the anterior complex (p = 0.006). An additional ROC analysis showed a good prediction for in-hospital mortality when taking the aneurysm's location into account [AUC.855 (CI.817 −0.893)].ConclusionsThe aneurysm's location proved to be a significant predictor of acute hydrocephalus, DCI, and in-hospital mortality, demonstrating the impact of this preexisting biological factor on the course of SAH.

Нарушение осмотического баланса в условиях нетравматического субарахноидального кровоизлияния

Актуальность. Аневризматическое субарахноидальное кровоизлияние является распространенным и серьезным заболеванием, которое может приводить к летальным последствиям. Цель исследования: изучить динамику натриемии в контексте ее клинико-патогенетического значения у пациентов с субарахноидальным кровоизлиянием. Материалы и методы. Обследовано 87 пациентов с субарахноидальным кровоизлиянием, из них 38 (43,68 %) — с изолированным субарахноидальным кровоизлиянием, 14 (16,09 %) — с субарахноидально-паренхиматозным, 29 (33,33 %) — с субарахноидально-желудочковым, 6 (6,9 %) — с субарахноидально-паренхиматозно-желудочковым кровоизлиянием, общее количество смешанных кровоизлияний составляло 56,32 %. Для проведения полного ангиографического исследования использовали ангиографический комплекс AXIOM Artis MP «Siemens». Результаты. Исследование SIADH-синдрома (синдром неадекватной секреции антидиуретического гормона) с развитием гипонатриемии у пациентов с субарахноидальным кровоизлиянием нетравматического генеза свидетельствует о тесной ассоциации между выраженностью нарушений осмотического гомеостаза и тяжестью клинического течения субарахноидального кровоизлияния согласно модифицированной шкале Fisher, шкале WFNS, шкале Нunt & Неss, шкале результатов GOSE (Glasgow Outcome Scale Extended) и обобщающей классификационной шкале для оценки прогноза исхода субарахноидального кровоизлияния (Ogilvy C.S. et Carter B.S.). У лиц с гипонатриемией на фоне субарахноидального кровоизлияния сопряженность сывороточного уровня натрия и показателя сывороточного уровня копептина адекватно и достоверно аппроксимируется уравнением регрессии логарифмического характера (по основанию 10), при значениях копептина более 0,70 нг/мл в более чем 50 % случаев регистрировалась натриемия средней тяжести. Выводы. Была обнаружена достоверная тесная взаимосвязь между уровнем данного пептида с нейроэндокринными свойствами — копептина и нарушением осмотического гомеостаза ионов натрия на фоне субарахноидального кровоизлияния с различной тяжестью клинического течения.

Arginase-1 Released into CSF After Aneurysmal Subarachnoid Hemorrhage Decreases Arginine/Ornithine Ratio: a Novel Prognostic Biomarker

We hypothesized that the enzyme arginase-1 is released into the cerebrospinal fluid (CSF) during red blood cell lysis and contributes to dysregulated metabolism of the nitric oxide (NO) precursor L-arginine during aneurysmal subarachnoid hemorrhage (SAH). This prospective case–control study included 43 patients with aneurysmal SAH and ventricular drainage for clinical reasons. Longitudinal CSF samples (99) were obtained in the course of SAH. Patients were dichotomized regarding the occurrence of cerebral vasospasm syndrome (CVS) (N = 19). Arginase-1 and the amino acids L-arginine and L-ornithine were quantified in CSF. Outcome assessments included delayed cerebral ischemia (DCI) and functional status after 3 months using the modified Rankin Scale (mRS). Arginase-1 was released into the CSF of SAH patients whereas this enzyme was undetectable in controls. Compared to patients without CVS, arginase-1 levels were higher in CVS patients until day 14 after clinical event. The well-known surrogate parameter for arginase acitivity, the L-arginine to L-ornithine ratio (Arg/Orn), correlated with CSF arginase-1 levels. Arg/Orn was reduced in patients with CVS from disease onset (days 1–3, p = 0.0009) until day 14. Logistic regression analysis of early Arg/Orn was predictive for CVS (p = 0.008) and DCI (p = 0.035), independent of age, Hunt and Hess grade, and intraventricular blood. Arg/Orn < 2.71 at disease onset predicted CVS with a sensitivity of 86.7% and specificity of 72.2%. Arg/Orn ≥ 2.71 predicted excellent functional outcome. We propose a novel mechanism contributing to NO deprivation during SAH: arginase-1 is released from erythrocytes into the CSF, leading to L-arginine consumption and reduced NO bioavailability. Furthermore, Arg/Orn is a robust predictor for occurrence of CVS, DCI, and functional outcome 3 months after aneurysmal SAH. Our data provide a novel prognostic biomarker and may contribute to the development of novel therapeutic strategies in SAH. Clinical Trial Registration-URL: http://www.drks.de. Unique identifier: DRKS00015293, date of registration: 13.09.2018.

Bilateral subdural hygromas after endovascular coiling for ruptured aneurysmal subarachnoid hemorrhage: an unusual and rare complication

ABSTRACTSubarachnoid hemorrhage (SAH) with subdural hygroma (SH) was rarely reported after endovascular coiling. A 60-year-old male presented with impaired consciousness and convulsions due to SAH from a ruptured aneurysm. It was managed by endovascular coiling 20 h after the onset of symptoms. Serial brain imaging for 2 weeks revealed progressive bilateral SHs, more on contralateral side of leaking aneurysm. Management of SH was discussed in a multidisciplinary setting to be conservative as there was neither significant mass effect nor hydrocephalus. The patient recovered neurologically except for mild dysarthria. The SH persisted for 2 months and then cleared gradually. We concluded that SH may arise and become symptomatic as an unusual sequela of post-coiling of a ruptured intracranial aneurysm, in which the SH can complicate the clinical course of SAH. However, the symptomatic SH may resolve spontaneously and completely without any intervention, but needs meticulous neurological assessment and follow-up.

Association of Early White Blood Cell Trend with Outcomes in Aneurysmal Subarachnoid Hemorrhage

An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0-3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17× 109 cells/L, SD 6.4 vs. 13.5× 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586-0.755) compared with each component alone. WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

Influence of aneurysm location on the clinical course of subarachnoid hemorrhage

Influence of aneurysm location on the clinical course of subarachnoid hemorrhage

Possibilities of mathematical definition of unfavourable course of subarachnoid haemorrhage in the acute period

Subarachnoid haemorrhage (SAH) is associated with a 30-day mortality rate of 50% and is one of the most life-threatening cerebrovascular diseases.&#x0D; Objective. Toevaluatetheprognosticsignificance and informativeness of some clinical indicators, highlighting the most optimal and reliable potential factors in the development of a mathematical equation for calculating the personal probability of complications in patients with subarachnoid hemorrhage of atraumatic etiology.&#x0D; Materials and methods. A clinical experimental study involved 87 patients with SAH, 44 were men, 43 – women. On the first day after SAH, half of the patients were hospitalized – 46 people (52,87%).&#x0D; Results. The constructed model for calculating the probability of events such as secondary ischemia, hydrocephalus, or cerebral vasospasm over the next 14 days indicates the correctness and adequacy of the constructed model of logistic regression.&#x0D; The personal probability of a complication is calculated by the formula: p = 1 / (1 + e-z), where p is the % probability of a complication of SAH; z = –45,5 + 17,5* Copeptine –0.44 × Na + 0,06 × Age + 1,99 × Ball (Hunt-Hess).&#x0D; Conclusions. The prognostic model allows us to consider that secondary ischemia and cerebral vasospasm are not only predictors of poor prognosis and potential factors for the formation of complications, but also are indicators for the correct determination of individual cumulative risk in SAH.

Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder. Neuroinflammation is a critical cause of brain injury following SAH in both acute and chronic phases. While accumulating evidence has shown that therapies targeting neuroinflammation exerted beneficial effects in experimental SAH, there is little clinical evidence. One of the factors making neuroinflammation complicated is that inflammatory signaling pathways and mediators act as protective or detrimental responses at different phases. In addition, biomarkers to detect neuroinflammation are little known in clinical settings. In this review, first, we discuss how the inflammatory signaling pathways contribute to brain injury and other secondary pathophysiological changes in SAH. Damage-associated molecular patterns arising from mechanical stress, transient global cerebral ischemia, red blood cell breakdown and delayed cerebral ischemia following SAH trigger to activate pattern recognition receptors (PRRs) such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and receptors for advanced glycation end products. Most of PRRs activate common downstream signaling transcriptional factor nuclear factor-κΒ and mitogen-activated protein kinases, releasing pro-inflammatory mediators and cytokines. Next, we focus on how pro-inflammatory substances play a role during the course of SAH. Finally, we highlight an important inducer of neuroinflammation, matricellular protein (MCP). MCPs are a component of extracellular matrix and exert beneficial and harmful effects through binding to receptors, other matrix proteins, growth factors, and cytokines. Treatment targeting MCPs is being proved efficacious in pre-clinical models for preventing brain injury including neuroinflammation in SAH. In addition, MCPs may be a candidate of biomarkers predicting brain injury following SAH in clinical settings.

Association Between Possible Osteoporosis and Shunt-Dependent Hydrocephalus After Subarachnoid Hemorrhage.

Background and Purpose- Pathological obstruction in arachnoid granulations after subarachnoid hemorrhage (SAH) can impede cerebrospinal fluid flow outward to the venous sinus and causing hydrocephalus. Because bone and arachnoid granulations share the same collagen type, we evaluated the possible relation between bone mineral density and shunt-dependent hydrocephalus after SAH. Methods- We measured Hounsfield units of the frontal skull on admission brain computed tomography in patients with SAH. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff Hounsfield unit in skull to predict osteopenia and osteoporosis in a large sample registry. According to the optimal cutoff skull Hounsfield unit values, study patients were then categorized as hypothetical normal, osteopenia, and osteoporosis. Odds ratios were estimated using logistic regression to determine whether the osteoporotic conditions are independent predictive factors for the development of shunt-dependent hydrocephalus after clipping for SAH. Results- A total of 447 patients (alive ≥14 days) with ruptured aneurysm SAH who underwent surgical clipping were retrospectively enrolled in this study during a 9-year period from 2 hospitals. We found that hypothetical osteoporosis was an independent predictor for shunt-dependent hydrocephalus after aneurysmal clipping for SAH after full adjustment for other predictive factors, including age (odds ratio, 2.08; 95% confidence interval, 1.06-4.08; P=0.032). Conclusions- Our study demonstrates a possible relation between possible osteoporosis and hydrocephalus after SAH. Hounsfield unit measurement on admission brain computed tomography may be helpful for predicting hydrocephalus during the clinical course of SAH in patients with osteoporosis or suspected osteoporosis.

Efficacy of endovascular treatment and feasibility of stent-assisted coiling in the presence of severe and symptomatic vasospasm

Background and purposeIn patients with aneurysmal subarachnoid hemorrhage, deciding the optimal treatment strategy is challenging in the presence of severe and symptomatic vasospasm and the existing literature is limited. The...

Dehydroepiandrosterone sulphate: diabolical hormone or epiphenomenon in aneurysmal subarachnoid hemorrhage?

Inflammation is purported to play an important role in the clinical course of subarachnoid hemorrhage. The current study by Höllig et al. entails using dehydroepiandrosterone sulfate, a hormone that inhibits key inflammatory pathways, as a predictor of functional outcome in these patients.

Microglia inflict delayed brain injury after subarachnoid hemorrhage.

Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.

Aneurysmal Subarachnoid Hemorrhage—Status Quo and Perspective

Aneurysmal subarachnoid hemorrhage (SAH) accounts for about 5 % of all strokes and continues to be a major cause of morbidity and mortality, especially in younger patients (mean age of 52). The global incidence of SAH is 9 per 100, 000 per year with some regional variations [1]. Data from population-based studies suggests a distinct decrease in case fatality (0.9 % per year) over the past four decades to about 30 %, which is likely originated in earlier and more advanced aneurysm repair as well as improved neurocritical care of SAH patients following aneurysm repair [2]. Nevertheless, the incidence of poor functional outcome in SAH patients remains high (about one third of patients). The main determinants for poor outcome after SAH are the degree of early brain injury (EBI) and the incidence of delayed cerebral ischemia (DCI) (see below) [3, 4]. The clinical course of SAH is complex and can be divided into an acute stage (the initial 72 h after SAH ictus) and a subacute stage, which lasts up until 20 days after SAH ictus. The potential main complications in the acute phase are EBI, rebleeding from the ruptured aneurysms, with a frequency of up to 23 % within the first 72 h, and acute hydrocephalus, occurring in about 20 % of the patients, whereas the main complications occurring in the subacute phase are DCI (formerly referred to as Bvasospasm,^ see below), cardiopulmonary or other medical complications, as well as permanent hydrocephalus [5–7]. The term EBI refers not only to direct mechanical damage to the brain tissue due to the hemorrhage but also to a cascade of different pathomechanisms, incl. a temporary increase of intracranial pressure, consecutive reduction of cerebral blood flow and/or microcirculatory spasm, transient global ischemia, neuronal injury or apoptosis, and edema formation [8]. The degree of EBI is a strong and independent predictor for clinical outcome after SAH [9, 3, 4]. The term DCI describes a complex phenomenon as a consequence of several pathomechanisms, incl. (1) macrovascular or angiographic vasospasm, i.e., narrowing of proximal cerebral arteries, (2) microvascular spasm, (3) microthromboembolism, (4) cortical spreading depolarization/ischemia, (5) autoregulatory dysfunction, and (6) inflammation [10–13, 7, 14–17]. The radiological term vasospasm has been widely replaced with the clinical term DCI, which describes a secondary neurological deterioration in the course SAH, excluding other causes of neurological deterioration; an explicit definition for DCI has been proposed by a multidisciplinary research group [16]. This Bparadigm shift^ came along with the insight that angiographic vasospasm occurs in up to 70 % of SAH patients, whereas only 30 % of SAH patients develop clinical features of DCI and, moreover, because pharmaceutical treatments exclusively targeting of angiographic vasospasm failed to improve neurological outcome after SAH [18–20]. However, in those clinical studies where cerebral infarction due to DCI was effectively reduced by experimental pharmaceutical treatments, a significant improvement of clinical outcome was also seen. These data further underlined the concept that DCI comprises several, pro-ischemic pathomechanisms, which ultimately result in cerebral infarction, but the individual importance of each of these pro-ischemic pathomechanisms remains to elucidated [21, 22]. The general shift in scientific focus, i.e., away from ‘vasospasm’ towards DCI and EBI, can also be * Nima Etminan etminan@uni-duesseldorf.de

Natural course of subarachnoid hemorrhage is worse in elderly patients.

Aging is a major risk factor for poor outcome in patients with ruptured or unruptured intracranial aneurysms (IA) submitted to treatment. It impairs several physiologic patterns related to cerebrovascular hemodynamics and homeostasis. Evaluate clinical, radiological patterns and prognostic factors of subarachnoid hemorrhage (SAH) patients according to age. Three hundred and eighty nine patients with aneurismal SAH from a Brazilian tertiary institution (Hospital do Servidor Público Estadual de São Paulo) were consecutively evaluated from 2002 to 2012 according to Fisher and Hunt Hess classifications and Glasgow Outcome Scale. There was statistically significant association of age with impaired clinical, radiological presentation and outcomes in cases of SAH. Natural course of SAH is worse in elderly patients and thus, proper recognition of the profile of such patients and their outcome is necessary to propose standard treatment.

Severe aortic stenosis and subarachnoid hemorrhage: Anesthetic management of lethal combination

Despite advances in various modalities of management, subarachnoid hemorrhage (SAH) continues to be associated with high mortality, which is further increased by associated comorbidities. Aortic stenosis (AS) is one such disease which can further complicate the course of SAH. We recently managed a known patient of severe AS, who presented with aneurysmal SAH. Patient was planned for eurovascular intervention. With proper assessment and planning, patient was managed with favorable outcome despite the restrictions faced in the neurovascular intervention laboratory.

Detection of symptomatic vasospasm after subarachnoid haemorrhage: initial findings from single time-point and serial measurements with arterial spin labelling

To detect symptomatic hemispheres during the postoperative course of subarachnoid haemorrhage (SAH) using arterial spin labelling (ASL). Eighteen patients with aneurysmal SAH were included; four exhibited symptomatic vasospasm postoperatively. All patients underwent ASL on days 9-10 (single time-point ASL). Nine patients underwent serial measurements of ASL (serial ASL) on days 1-2, 9-10 and 13-21, and seven patients also underwent imaging on days 4-7. CBF in the posterior part of the MCA territory was measured, and the ipsilateral/contralateral ratio of CBF was calculated. Differences between symptomatic hemispheres and others underwent ROC analysis. Single time-point ASL revealed that CBF(day9-10) and CBF(i/c_day9-10) were significantly lower in symptomatic hemispheres than in asymptomatic hemispheres (P < 0.001). Serial ASL was significantly decreased on CBF(day4-7) compared with CBF(day1-2) and on CBF(day9-10) compared with CBF(day4-7), and significantly increased on CBF(day13-21) compared with CBF(day9-10). ROC analysis of single time-point ASL revealed that AUC for CBF(day9-10) was 0.95, significantly higher than CBF(i/c_day9-10) (P < 0.001). ROC analysis of serial ASL showed that AUC for CBF(day9-10) was 0.93 and significantly higher than CBF(day9-10/day1-2) and CBF(i/c_day9-10) (P < 0.001). Single time-point ASL revealed significant CBF reduction in symptomatic hemispheres compared with asymptomatic hemispheres. Serial ASL showed time-dependent CBF changes after SAH. • MR arterial spin labelling (ASL) can non-invasively assess cerebral blood flow (CBF) • ASL revealed significant CBF reduction in symptomatic hemispheres compared with asymptomatic hemispheres • Serial ASL measurements enable observation of time-dependent CBF changes after SAH • ASL is non- invasive and suitable for serial repeated examinations.

Interleukin-1&amp;bgr; Increases Release of Endothelin-1 and Tumor Necrosis Factor as Well as Reactive Oxygen Species by Peripheral Leukocytes During Experimental Subarachnoid Hemorrhage

In the subarachnoid hemorrhage (SAH) blood mixes with cerebrospinal fluid, what starts immunoinflammatory processes - increased synthesis of proinflammatory cytokines, and formation of reactive oxygen species (ROS), resulting in pre-activation of different populations of peripheral leukocytes. Migration of leukocytes to the brain parenchyma through broken blood brain barrier may produce extra brain tissue injury besides of that resulting from SAH. We examined in adult rats the effect of interleukin-1β (IL-1β) neutralization on secretion of cytokines as well as production of ROS in the course of SAH. SAH was produced by injection of 150 μL of autologous arterial blood into cisterna magna. In 50% of animals, IL-1beta activity was inhibited by intracerebroventricular administration of anti-rat IL-1β antibodies. Ninety minutes or 24 hrs following surgery, blood samples were drawn from the extraorbital plexus and centrifuged to obtain two leukocyte subpopulations - polymorphonuclear (PMN) and mononuclear (MN). The chemiluminescence, a hallmark of ROS synthesis, was measured in PMNs. In supernatants from MNs cultures, concentrations endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed. SAH caused the increase ofn PMNs chemiluminescence as well as the increase of production of ET-1 and TNF-α by MNs but had no influence on IL-6 concentration. Neutralization of IL-1β resulted in significant decrease of chemiluminescence as well as concentration of both ET-1 and TNF-α, while IL-6 concentration was increased. These revealed an important role of IL-1β in the activation of peripheral leukocytes in the course of subarachnoid hemorrhage.

Elevated Peripheral Neutrophils and Matrix Metalloproteinase 9 as Biomarkers of Functional Outcome Following Subarachnoid Hemorrhage

There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (N = 55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6–8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0–14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (N = 35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (p = 0.0003) and neutrophil (p = 0.0002) counts during post-SAH days 0–14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2–3, p = 0.018), blood MMP-9 (post-SAH days 4–5, p = 0.045), and CSF MMP-9 (post-SAH days 2–3, p = 0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6–8, R = 0.39; p = 0.055; post-SAH days 10–14, R = 0.79; p < 0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4–5, R = 0.72; p = 0.0002). Elevation of CSF MMP-9 during post-SAH days 0–14 is associated with poor 3-month outcome (p = 0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.

Outcomes of endovascular coiling of anterior communicating artery aneurysms in the early post-rupture period: A prospective analysis

There have been significant advances in the technical aspects of endovascular therapy of cerebral aneurysms. Anterior communicating artery (Acom A) aneurysms were traditionally treated by surgical clipping. Endovascular coiling has the distinct advantage of being minimally invasive and can be performed anytime during the course of subarachnoid hemorrhage (SAH). To evaluate the results of endovascular coiling of Acom A aneurysms in the early post-rupture period. Between June 1999 and December 2009, 103 Acom A aneurysms were treated with endovascular coiling. All the patients underwent digital subtraction angiography (DSA) and a diagnostic 3D rotational angiogram (3D-RA), followed by coiling using dedicated intracranial coils. Of the 103 patients coiled, 52% presented in Fischer grade 3/4 SAH and 13.5% in Hunt and Hess grade 4/5. Technical success was 98%. Complete obliteration of the aneurysm was achieved in 97 (94%) patients. Only one patient died of direct procedure-related complication due to coil prolapse. None of the patients had rebleeds. Six-month check angiogram performed in 34 patients showed significant recanalization in one patient. Ruptured Acom A aneurysms are implicated in majority of cases of SAH. Our results support the latest guideline "that endovascular coil occlusion of the aneurysm is appropriate for patients with a ruptured cerebral artery aneurysm that is deemed treatable either by endovascular coiling or by surgical clipping."