Hours Of Subarachnoid Hemorrhage Research Articles

Abstract TP319: Time Course of Novel Hypothalamic Protein Sushi Repeat-Containing Protein X- Linked 2 Expression in a Rat Model of Subarachnoid Hemorrhage

Background: Hypothalamic injury after subarachnoid hemorrhage (SAH) is known to be associated with short- and long-term prognosis. Recently, a novel hypothalamic protein, Sushi repeat-containing protein X-linked 2 (SRPX2), was reported as a potential biomarker for hypothalamic damage after traumatic brain injury. However, there are no reports on SRPX2 in SAH, and its role is unknown. In this study, we investigated the expression of SRPX2 in the hypothalamus after SAH using a rat model of SAH. Methods: We made endovascular perforation model of SAH using 300g - 450g SD rats, and they were divided into two groups: Sham operated and SAH group. The endpoints were 3, 6, 12, 24, and 72 hours after SAH, and 7 days and 4 weeks after SAH, and physiological findings and neurological symptoms were measured. In addition, changes in SRPX-2 in the hypothalamic injury and related factors were examined immunohistochemically. Results: The SAH group showed significant neurological deterioration, and a significant decrease in body temperature after 3 h of SAH. Expression of SRPX2 in the hypothalamus was also significantly decreased at 3 h after SAH. However, it was not associated with changes in FJC- and TUNEL-positive cells suggestive of cell death or DHE expression suggestive of oxidative stress. On the other hand, OXT showed a significant decrease after 3 hours of SAH as measured by ELISA in serum from the jugular vein. Conclusions: This is the first study to investigate the expression of SRPX2 in the hypothalamus after SAH time course. Although our results suggest that SRPX2 may not be directly associated with hypothalamic injury after SAH, the fact that SRPX2 expression was decreased during the hyperacute phase and OXT and body temperature were also decreased at the same time suggests that SRPX2 may be indirectly associated with hypothalamic injury after SAH through regulation of endocrine and autonomic function in the hypothalamic-pituitary axis. Further studies are warranted to investigate the possibility that SRPX2 may be indirectly related to hypothalamic disturbances after SAH through endocrine and autonomic regulation of the hypothalamic-pituitary axis.

Roles of glutamate in brain injuries after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a stroke type with a high rate of mortality and morbidity. Post-SAH brain injury as a determinant of poor outcome is classified into the following two types: early brain injury (EBI) and delayed cerebral ischemia (DCI). EBI consists of various acute brain pathophysiologies that occur within the first 72 hours of SAH in a clinical setting. The underlying mechanisms of DCI are considered to be cerebral vasospasm or microcirculatory disturbance, which develops mostly 4 to 14 days after clinical SAH. Glutamate is the principal neurotransmitter in the central nervous system, but excessive glutamate is known to induce neurotoxicity. Experimental and clinical studies have revealed that excessive glutamates are released after SAH. In addition, many studies have reported the relationships between excessive glutamate release or overactivation of glutamate receptors and excitotoxicity, cortical spreading depolarization, seizure, increased blood-brain barrier permeability, neuroinflammation, microthrombosis formation, microvasospasm, cerebral vasospasm, impairments of brain metabolic supply and demand, impaired neurovascular coupling, and so on, all of which potentially contribute to the development of EBI or DCI. As glutamates always exert their functions through one or more of 4 major receptors of glutamates, it would be valuable to know the mechanisms as to how glutamates cause these pathologies, and the possibility that a glutamate receptor antagonist may block the pathologies. To prevent the mechanistic steps leading to glutamate-mediated neurotoxicity may ameliorate SAH-induced brain injuries and improve the outcomes. This review addresses the current knowledge of glutamate-mediated neurotoxicity, focusing on EBI and DCI after SAH.

Safety and Efficacy of Endovascular Embolization of Ruptured Intracranial Aneurysms within 72 hours of Subarachnoid Hemorrhage.

The purpose of the study was to investigate the safety and efficacy of endovascular embolization of ruptured intracranial aneurysms within 72 hours of subarachnoid hemorrhage (SAH). Patients with intracranial aneurysms treated with embolization were divided into group A (n = 277), patients with ruptured aneurysms treated within 72 hours of SAH; group B (n = 138), patients with ruptured aneurysms treated beyond 72 hours; and group C (n = 93), patients with unruptured aneurysms. Embolization was successful in all but four patients (99.2%). The periprocedural complication rate was 36.2% in group B, significantly (p < 0.05) greater than that in group A (24.5%) or group C (11.8%). The rebleeding rate was 9.7% (6/62 patients) in groups A and B after embolization and only 0.3% (1/346 patients) in aneurysms with total or subtotal occlusion. Of these three groups of patients, 69.7% in group A, 58.7% in group B, and 76.3% in group C achieved Glasgow Outcome Scale (GOS) score of 5 or modified Rankin Scale (mRS) score of 0- to 1 at discharge. A significant difference (p < 0.05) existed in the clinical outcome between the three groups. The percentages of patients without deficits (GOS 5 or mRS 0-1) and slight disability (mRS 2) were 80.2% in group A, 81.2% in group B, and 96.7% in group C. The mortality rate was 4.3% (12/277 patients) in group A and 7.2% (10/138 patients) in group B with no significant (p = 0.21) difference. Follow-up was performed at 3 to 54 months (mean 23.2), and the recanalization rate was 28.6% (32/112 patients) in group A, 22.4% (11/49 patients) in group B, and 28.6% (16/56 patients) in group C, with no significant differences (p = 0.15). Hydrocephalus occurred in 30.5% (39/128 patients) in group B, which was significantly (p < 0.01) greater than that in group A (9.4%) or group C (2.2%). Early embolization of ruptured cerebral aneurysms within 72 hours of rupture is safe and effective and can significantly decrease periprocedural complications compared with management beyond 72 hours. Timely management of cisternal and ventricular blood can reduce hydrocephalus incidence and improve prognosis.

TRATAMIENTO DEFINITIVO DE ANEURISMAS CEREBRALES EN EL HOSPITAL NACIONAL CAYETANO HEREDIA EN LIMA PERÚ: RESULTADOS DE UNA SERIE DE CASOS

Objectives: Subarachnoid hemorrhage (SAH) due to rupture of a cerebral aneurysm continues to be a disease with high morbidity and mortality in our setting, despite advances in microsurgery and endovascular therapy. The objective of the present study was to determine the demography, vascular territory, and complications that occur in the perioperative management of patients with ruptured cerebral aneurysms treated at the Cayetano Heredia Hospital. Methods: An observational descriptive study of patients with cerebral aneurysm undergoing surgical and endovascular treatment was carried out in the Neurosurgery Service of the Cayetano Heredia Hospital from 2016 to 2018. The clinical records and operative reports were reviewed. Results: In a period of 30 months, definitive treatment was performed in 56 patients with a diagnosis of a ruptured cerebral aneurysm, of which 5 received endovascular treatment and 51 treatment by craniotomy and clipping. 62.5% were women, and 50% of the total were between the fifth and sixth decade of life. In more than 50% of cases, treatment was performed within 96 hours of SAH. Regarding the affected arterial territory, 15 patients (27%) had an aneurysm of the territory of the anterior communicating (AComA) and another 15 (27%) in the posterior communicating artery (PComA). Mortality was 17.8%, 70% being due to direct causes such as cerebral infarction and severe vasospasm. Conclusions: The treatment of the aneurysms was mainly by microsurgery, the aneurysms of the AComA, PComA, and middle cerebral (MCA) had a similar proportion and, in more than 50% the treatment was carried out in the first 4 days. More state support is required to increase endovascular therapy and obtain more promising results. Keywords: Intracranial Aneurysm, Microsurgery, Craniotomy, Endovascular Procedures (source: MeSH NLM)

Experience of using low-profile braided stents for the treatment of ruptured intracranial aneurysms in the first 72 hours of subarachnoid hemorrhage

The study objective is to present our experience in the treatment of ruptured cerebral aneurysms using intracranial low-profile braided stents in the first 72 hours of subarachnoid hemorrhage. Materials and methods . A retrospective analysis of 5 patients’ data was performed. All patients were treated for a ruptured cerebral aneurysm in the period from June 2017 to December 2018 at the Surgut Clinical Hospital for Traumatology. Patients were operated using a low-profile braided stent in the first 72 h of subarachnoid hemorrhage. Clinical data, Hunt—Hess grade, morphology of aneurysms, Raymond— Roy angiographic results, outcomes according to a modified Rankin Scale were evaluated. Results. All 5 aneurysms are turned off from the bloodstream in the first 72 hours from rupture. The preoperative condition was assessed as mild in 1 patient (Hunt—Hess grade I—II), moderate in 3 (grade III), and ssevere in 1 (grade IV). Stent placement was used to “bail out" situations with coil migration saccular aneurysm (n = 2), for occlusion the broad-based aneurysms (n = 2), for dissecting neurysm occlusion without of coils using (n = 1). Total aneurysm occlusion was achieved in 4 cases (Raymond—Roy I), subtotal in 1 (Raymond—Roy II). Technical difficulties were in 1 case: transient intraoperative in-stent thrombosis, regressed with the super-selective administration of tissue plasminogen activator. A follow-up angiographies demonstrated complete aneurysm occlusion in 4 cases, including “solo" stent placement (Raymond—Roy I); recurrent aneurysm occurred in 1 (Raymond—Roy III), retreatment was required. The favorable outcome of treatment (modified Rankin Scale 0—2) was achieved in 5 cases. Conclusion. The use of low-profile braided stents for occlusion ruptured cerebral aneurysms in the first 72 hours of subarachnoid hemorrhage is relatively safe and can be used to prevent re-rupture. However, it could be associated with a relatively high risk of periprocedural thromboembolism.

Commentary on the article of E.O. Ivankova, V.V. Darvin, M.A. Bessmertnykh “Experience of using low-profile braided stents for the treatment of ruptured intracranial aneurysms in the first 72 hours of subarachnoid hemorrhage”

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Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage.

Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms. In this study, a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats. Z-IETD-FMK (0.5, 1, 2 mg/kg; an inhibitor of caspase-8) was delivered via intravenous (tail vein) injection immediately after subarachnoid hemorrhage. After 12 hours of subarachnoid hemorrhage, western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours, peaked at 24 hours, and then decreased at 72 hours after subarachnoid hemorrhage. Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage. Z-IETD-FMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage. The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21-27 days after subarachnoid hemorrhage. Furthermore, inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3, caspase-1, and interleukin-1β after subarachnoid hemorrhage. In conclusion, our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University, China (approval No. 2016-193) on February 25, 2016.

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. Materials and methods: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor- kappa B (NF-κB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat brain were examined by ELISA. Results: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-κB p65, COX-2, TNF-α, and IL-1β, all of which were inhibited by LY294002. Conclusion: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.

Annexin A7 induction of neuronal apoptosis via effect on glutamate release in a rat model of subarachnoid hemorrhage.

Glutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms. Endovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction. ANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression. ANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.

Impaired microcirculation after subarachnoid hemorrhage in an in vivo animal model

The influence of aneurysmal subarachnoid hemorrhage (SAH) on brain microcirculation has not yet been systematically investigated. We established an animal model to examine (1) the brain surface microcirculation (2) the influences of cerebrospinal fluid (CSF) from aneurysmal SAH on the brain surface microcirculation. A rat SAH model was induced by injection of autologous arterial blood into the cisterna magnum, and the brain surface microcirculation was evaluated by a capillary videoscope with craniotomy at the fronto-parietal region. CSF from SAH rats and SAH patients was applied on the brain surface of naïve rats to assess the resulting microcirculatory changes. In the SAH rats, diffuse constriction of cortical arterioles within 24 hours of SAH was observed. Similar patterns of microcirculation impairment were induced on normal rat brain surfaces via application of CSF from SAH rats and SAH patients. Furthermore, the proportion of subjects with arteriolar vasoconstriction was significantly higher in the group of SAH patients with delayed ischemic neurological deficits (DIND) than in those without DIND (p < 0.001). This study demonstrated impaired microcirculation on brain surface arterioles in a rat model of SAH. CSF from SAH rats and patients was responsible for impairment of brain surface microcirculation.

Clinical characteristics and outcome of aneurysmal subarachnoid hemorrhage with intracerebral hematoma.

OBJECTIVE Intracerebral hematoma (ICH) with subarachnoid hemorrhage (SAH) indicates a unique feature of intracranial aneurysm rupture since the aneurysm is in the subarachnoid space and separated from the brain by pia mater. Broad consensus is lacking regarding the concept that ultra-early treatment improves outcome. The aim of this study is to determine the associative factors for ICH, ascertain the prognostic value of ICH, and investigate how the timing of treatment relates to the outcome of SAH with concurrent ICH. METHODS The study data were pooled from the SAH International Trialists repository. Logistic regression was applied to study the associations of clinical and aneurysm characteristics with ICH. Proportional odds models and dominance analysis were applied to study the effect of ICH on 3-month outcome (Glasgow Outcome Scale) and investigate the effect of time from ictus to treatment on outcome. RESULTS Of the 5362 SAH patients analyzed, 1120 (21%) had concurrent ICH. In order of importance, neurological status, aneurysm location, aneurysm size, and patient ethnicity were significantly associated with ICH. Patients with ICH experienced poorer outcome than those without ICH (OR 1.58; 95% CI 1.37-1.82). Treatment within 6 hours of SAH was associated with poorer outcome than treatment thereafter (adjusted OR 1.67; 95% CI 1.04-2.69). Subgroup analysis with adjustment for ICH volume, location, and midline shift resulted in no association between time from ictus to treatment and outcome (OR 0.99; 95% CI 0.94-1.07). CONCLUSIONS The most important associative factor for ICH is neurological status on admission. The finding regarding the value of ultra-early treatment suggests the need to more robustly reevaluate the concept that hematoma evacuation of an ICH and repair of a ruptured aneurysm within 6 hours of ictus is the most optimal treatment path.

Randomized pilot trial of intensive management of blood pressure or volume expansion in subarachnoid hemorrhage (IMPROVES).

Volume expansion and hypertension are widely used for the hemodynamic management of patients with subarachnoid hemorrhage. To investigate the feasibility, adherence, and retention in a trial of volume expansion and blood pressure manipulation to prevent delayed cerebral ischemia. A randomized pilot trial using a 2-way factorial design allocating patients within 72 hours of subarachnoid hemorrhage to either normovolemia (NV) or volume expansion (HV) and simultaneously to conventional (CBP) or augmented blood pressure (ABP) for 10 days. The study endpoints were protocol adherence and retention to follow-up. The quality of endpoints for a larger trial were 6-month modified Rankin Scale score, comprehensive neurobehavioral assessment, delayed cerebral ischemia, new stroke, and discharge disposition. Twenty patients were randomized and completed follow-up. The overall difference in daily mean intravenous fluid intake was 2099 mL (95% confidence interval [CI]: 867, 3333), HV vs NV group. The overall mean systolic blood pressure difference was 5 mm Hg (95% CI: -4.65, 14.75), ABP vs CBP group. Adverse events included death (n=1), delayed cerebral ischemia (n=1), and pulmonary complications (n=3). There were no differences in modified Rankin Scale score between HV and NV (difference 0.1; 95% CI: -1.26, 1.46, P=.87) or between ABP and CBP groups (-0.5, 95% CI: -1.78, 0.78, P=.43). Neuropsychological scores were similar between HV vs NV, but tended to be worse in ABP (57±27) vs CBP group (85±21, P=.04). This pilot study showed adequate feasibility and excellent retention to follow-up. Given the suggestion of possible worse neurobehavioral outcome with ABP, a larger trial to determine the optimal blood pressure management in this patient population is warranted. (ClinTrials.gov NCT01414894.)

Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: Mechanism and Therapies

Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: Mechanism and Therapies

Impact of Ultra-early Coiling on Clinical Outcome after Aneurysmal Subarachnoid Hemorrhage in Elderly Patients

The incidence of aneurysmal subarachnoid hemorrhage is increasing in the elderly as life expectancy increases. The purpose of this study was to analyze whether ultra-early coiling of ruptured intracranial aneurysms improves clinical outcomes in elderly patients. Records of patients (aged ≥ 70 years) with aneurysmal subarachnoid hemorrhage treated with endovascular coiling were retrieved. Patients were classified into two groups: group A (patients coiled within 24 hours of subarachnoid hemorrhage) and group B (patients coiled ≥24 hours after subarachnoid hemorrhage). For each group, patient demographics, World Federation of Neurological Surgeons clinical grade, Fisher computed tomographic grade, aneurysm characteristics, and clinical outcomes were recorded. Outcomes were measured using the Modified Rankin Scale at 6 months. Fifty-six patients were coiled within 24 hours of subarachnoid hemorrhage (group A) and 40 patients at ≥24 hours after subarachnoid hemorrhage (group B). Groups A and B had similar clinical and angiographic characteristics. Clinical outcomes showed that a total of 87.5% of patient (49 of 56) in group A were independent (Modified Rankin Scale score 0-2) compared with 70.0% of patients (28 of 40) in group B (P = .034). In multivariate logistic regression analysis, ultra-early coiling (odds ratio, 3.860; 95% confidence interval, 1.125-13.249; P = .032) proved to be an independent predictor of better clinical outcome (Modified Rankin Scale score 0-2). Ultra-early (<24 hours after subarachnoid hemorrhage) coiling of ruptured aneurysms was marginally associated with improved clinical outcomes compared to coiling at ≥24 hours in elderly patients. Larger, prospective studies are required to adequately assess outcome differences between these two groups.

Does Treatment of Ruptured Intracranial Aneurysms Within 24 Hours Improve Clinical Outcome?

The purpose of this study was to analyze whether treating ruptured intracranial aneurysms within 24 hours of subarachnoid hemorrhage improves clinical outcome. An 11-year database of consecutive ruptured intracranial aneurysms treated with endovascular coiling or craniotomy and clipping was analyzed. Outcome was measured by the modified Rankin Scale at 6 months. Our policy is to treat all cases within 24 hours of subarachnoid hemorrhage. Treatment delays are due to nonclinical logistical factors. Two hundred thirty cases were coiled or clipped within 24 hours of subarachnoid hemorrhage and 229 at >24 hours. No difference in age, gender, smoking, family history of subarachnoid hemorrhage, aneurysm size, or aneurysm location was found between the groups. Poor World Federation of Neurological Surgeons clinical grade patients were overrepresented in the ultra-early group. Increasing age and higher World Federation of Neurological Surgeons clinical grade were predictors of poor outcome. Eight point zero percent (16 of 199) of cases treated within 24 hours of SAH (ultra-early) were dependent or dead at 6 months compared with 14.4% (30 of 209) of those treated at >24 hours post-SAH (delayed; (χ2, P0.044) [corrected]. A total of 3.5% of cases coiled within 24 hours were dependent or dead at 6 months compared with 12.5% of cases coiled at 1 to 3 days, an 82% relative risk reduction and a 10.2% absolute risk reduction (χ2, P=0.040). These groups did not differ in age, World Federation of Neurological Surgeons clinical grade, aneurysm size, or aneurysm location. Treatment of ruptured aneurysms within 24 hours is associated with improved clinical outcomes compared with treatment at >24 hours. The benefit is more pronounced for coiling than clipping.

Variation of patient characteristics, management, and outcome with timing of surgery for aneurysmal subarachnoid hemorrhage.

The past 30 years have seen a shift in the timing of surgery for aneurysmal subarachnoid hemorrhage (SAH). Earlier practices of delayed surgery that were intended to avoid less favorable surgical conditions have been replaced by a trend toward early surgery to minimize the risks associated with rebleeding and vasospasm. Yet, a consensus as to the optimal timing of surgery has not been reached. The authors hypothesized that earlier surgery, performed using contemporary neurosurgical and neuroanesthesia techniques, would be associated with better outcomes when using contemporary management practices, and sought to define the optimal time interval between SAH and surgery. Data collected as part of the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) were analyzed to investigate the relationship between timing of surgery and outcome at 3 months post-SAH. The IHAST enrolled 1001 patients in 30 neurosurgical centers between February 2000 and April 2003. All patients had a radiographically confirmed SAH, were World Federation of Neurosurgical Societies Grades I-III at the time of surgery, and underwent surgical clipping of the presumed culprit aneurysm within 14 days of the date of hemorrhage. Patients were seen at 90-day follow-up visits. The primary outcome variable was a Glasgow Outcome Scale score of 1 (good outcome). Intergroup differences in baseline, intraoperative, and postoperative variables were compared using the Fisher exact tests. Variables reported as means were compared with ANOVA. Multiple logistic regression was used for multivariate analysis, adjusting for covariates. A p value of less than 0.05 was considered to be significant. Patients who underwent surgery on Days 1 or 2 (early) or Days 7-14 (late) (Day 0 = date of SAH) fared better than patients who underwent surgery on Days 3-6 (intermediate). Specifically, the worst outcomes were observed in patients who underwent surgery on Days 3 and 4. Patients who had hydrocephalus or Fisher Grade 3 or 4 on admission head CT scans had better outcomes with early surgery than with intermediate or late surgery. Early surgery, in good-grade patients within 48 hours of SAH, is associated with better outcomes than surgery performed in the 3- to 6-day posthemorrhage interval. Surgical treatment for aneurysmal SAH may be more hazardous during the 3- to 6-day interval, but this should be weighed against the risk of rebleeding.

Brain edema formation and neurological impairment after subarachnoid hemorrhage in rats

Global cerebral edema is an independent risk factor for early death and poor outcome after subarachnoid hemorrhage (SAH). In the present study, the time course of brain edema formation, neurological deficits, and neuronal cell loss were investigated in the rat filament SAH model. Brain water content and neurological deficits were determined in rats randomized to sham (1-, 24-, or 48-hour survival), SAH by endovascular perforation (1-, 24-, or 48-hour survival), or no surgery (control). The neuronal cell count (CA1-3) was quantified in a separate set of SAH (6-, 24-, 48-, or 72-hour survival) and shamoperated animals. Brain water content increased significantly 24 (80.2 +/- 0.4% [SAH] vs 79.2 +/- 0.1% [sham]) and 48 hours (79.8 +/- 0.2% [SAH] vs 79.3 +/- 0.1% [sham]) after SAH. The neuroscore was significantly worse after SAH (33 +/- 15 [24 hours after SAH] vs 0 +/- 0 points [sham]) and correlated with the extent of brain edema formation (r = 0.96, p < 0.001). No hippocampal damage was present up to 72 hours after SAH. Brain water content and neurological dysfunction reached a maximum at 24 hours after SAH. This time point, therefore, seems to be optimal to test the effects of therapeutic interventions on brain edema formation. Neuronal cell loss was not present in CA1-3 up to 72 hours of SAH. Therefore, morphological damage needs to be evaluated at later time points.

ADMISSION ANGIOGRAPHIC CEREBRAL CIRCULATION TIME MAY PREDICT SUBSEQUENT ANGIOGRAPHIC VASOSPASM AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

Angiographic cerebral vasospasm occurs in approximately 70% of patients hospitalized after aneurysmal subarachnoid hemorrhage (SAH) and is associated with poor outcome. In this study, we examined whether or not cerebral circulation time (CCT) measured with digital subtraction angiography was associated with angiographic vasospasm. Patients who underwent cerebral angiography within 24 hours of SAH were analyzed. Contrast dye transit time from the arterial to the venous phase was measured to obtain CCT (supraclinoid internal carotid artery to parietal cortical veins) and microvascular CCT (cortical middle cerebral artery to parietal cortical veins). Patients with ruptured anterior circulation aneurysms and vasospasm on follow-up angiography (Group A) were compared with patients with SAH without vasospasm (Group B) and with normal control subjects (Group C). There were 20 patients in Group A (mean age, 51 +/- 13 yr), 17 patients in Group B (56 +/- 12 yr), and 98 patients in Group C (52 +/- 12 yr). CCT in patients in Group A (7.7 +/- 1.9 s) was significantly longer than those in Groups B (6.6 +/- 1.2 s; P = 0.005) and C (5.9 +/- 1 s; P < 0.001). Microvascular CCT in patients in Group A (7.1 +/- 1.8 s) was significantly longer than those in Groups B (6.1 +/- 1.2 s; P = 0.003) and C (5.4 +/- 0.9 s; P < 0.001). Prolonged CCT, a measurement of increased small vessel resistance, can be identified within 24 hours after SAH and is associated with subsequent angiographic vasospasm. These results suggest that microcirculation changes may be involved in vasospasm.

CT Perfusion-Derived Mean Transit Time Predicts Early Mortality and Delayed Vasospasm after Experimental Subarachnoid Hemorrhage

There are limited indicators available to predict cerebral vasospasm in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to determine if CT perfusion-derived hemodynamic parameters are predictors of vasospasm severity and outcome after experimental SAH. SAH was induced in 25 New Zealand white rabbits. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were measured with CT perfusion before SAH, within 1 hour after SAH, and on days 2, 4, 7, 9, and 16 after SAH. Basilar artery diameter, measured with CT angiography and neurologic scoring, was also obtained on the same days. Differences between animals with moderate-severe delayed vasospasm (>/=24% basilar artery narrowing) and mild delayed vasospasm (<24% basilar artery narrowing) were investigated with repeated measures analysis of variance. Multiple linear regression analysis was used to investigate the relationship between CT perfusion parameters (CBF, CBV, MTT), basilar artery diameter, and neurologic score. MTT increase <1 hour after SAH independently predicted mortality within 48 hours of SAH (P < .05). MTT and neurologic deficits were significantly greater with moderate-severe than with mild vasospasm (P < .05). MTT on day 2, but not CBF or CBV, was a significant predictor of subsequent moderate-severe delayed vasospasm (P < .05). In the rabbit model of experimental SAH, the CT-derived hemodynamic parameter MTT on day 0 predicted early mortality, and MTT on day 2 predicted development of moderate-severe delayed vasospasm. MTT was also significantly correlated with arterial diameter and neurologic score.

Troponin I in predicting cardiac or pulmonary complications and outcome in subarachnoid haemorrhage

Background: Patients with aneurysmal subarachnoid haemorrhage (SAH) are at risk of cardiac and pulmonary complications. Troponin I (cTnI), a reliable marker of myocardial injury, is frequently raised after SAH. Aims:...