Acute Phase Of Subarachnoid Hemorrhage Research Articles

Evaluation of flow diverter use in acutely ruptured vertebral artery dissecting Aneurysms: A focus on safety and efficacy for rapid Aneurysm obliteration

ObjectiveFlow diverter device (FDD) has emerged as the reconstruction technique for treating ruptured dissecting vertebral artery Aneurysms (VADA), but data on feasibility regarding re-rupture risk and timing of Aneurysm obliteration following FDD treatment is still limited. Therefore, this study aimed to evaluate the safety and efficacy of FDD in the treatment of VADAs presenting with subarachnoid hemorrhage (SAH). MethodsWe retrospectively reviewed patients with ruptured VADA presenting with subarachnoid hemorrhage who underwent FDD placement at our institution between 2015 and 2023. Patient demographic data, Aneurysm configuration, and occlusion status were analyzed. ResultsThirteen patients with SAH from VADA rupture underwent FDD implantation. The average size of the largest diameter of the Aneurysm was 11.2 mm (range 6.5–21 mm). Eight of 13 (61.5 %) patients had their Aneurysms completely obliterated within 2 weeks after the procedure. The small dissecting Aneurysm (d = 0.636, p = 0.002) and degree of intra-Aneurysmal contrast stasis (d = 0.524, p = 0.026) were associated with rapid Aneurysm occlusion, according to the Somer’s d coefficient. There were no ischemic or hemorrhagic complications at the average clinical follow-up of 28.4 months (range 5–67 months) and average angiographic follow-up of 20.1 months (range 3–60 months). A favorable outcome (mRS 0–2) was achieved in 12 patients (92.3 %). ConclusionsFDD is safe and effective for the reconstruction of acutely ruptured VADAs. In addition, our study emphasizes that small dissecting Aneurysms tend to be rapidly obliterated after flow diversion, which eliminates the risk of re-rupture during the acute phase of subarachnoid hemorrhage.

Abstract TP318: Evaluating Hypothalamic Injury in a Rat Model of Subarachnoid Hemorrhage

Background and purpose: Hypothalamus is one of the most affected parts of the brain by subarachnoid hemorrhage (SAH). There are some reports that hypothalamic disorders are important determinants of poor prognosis after SAH from acute to chronic phase. However, there have never been any reports on the development of therapeutic strategies targeting the hypothalamus for SAH, and few reports have even demonstrated immunohistological evidence of hypothalamic injury after SAH. Here, we demonstrated on the investigation of temporal changes in hypothalamic injury from the hyperacute phase to the chronic phase after SAH in a rat model of SAH. Methods: Moderate to severe endovascular perforation model of SAH was created using 300g - 450g Sprague-Dawley 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 and hypothalamic injury and related factors in the hypothalamus were studied immunohistochemically. Results: The SAH group showed significant neurological deterioration, and the expression of FJC, indicative of cell death, and TUNEL-positive cells, indicative of apoptosis, in the hypothalamus was significantly elevated in the early phase and decreased over time compared to the sham SAH group. On the other hand, oxytocin, a hypothalamic hormone associated with neuronal protection, was significantly decreased in the SAH group during the acute phase. Conclusions: The present study shows that hypothalamic injury appears hyper acute phase of SAH and persists at least during the acute phase of SAH. These findings suggest that the hypothalamus may be an important therapeutic target in the acute phase of SAH.

Nonconvulsive status epilepticus in patients with acute subarachnoid hemorrhage is associated with negative arterial spin labeling on peri-ictal magnetic resonance images

PurposeNon-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase. MethodsBased on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics. ResultsIn 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %). ConclusionNormal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness.

Initial Treatment of Subarachnoid Hemorrhage

The re-rupture of a subarachnoid hemorrhage(SAH)due to a ruptured cerebral aneurysm is a poor prognostic factor, and initial treatment to prevent re-rupture is important in the acute phase of SAH. Prevention of re-rupture is performed by reducing blood pressure, by sedation, and by analgesia until the patient undergoes radical surgery. It is recommended that the systolic blood pressure be lowered to below 120-140 mmHg. When SAH is suspected, a head CT scan should be obtained after the initial treatment. If the SAH is not clearly visible on CT but is strongly suspected, MRI should be performed. Once a SAH is diagnosed, three-dimensional CT angiography should be performed to search for cerebral aneurysms. SAHs may also cause breathing and circulation problems due to neurogenic pulmonary edema and Takotsubo cardiomyopathy. Clipping is more curative than coil embolization, but coil embolization has been shown to have better long-term survival and independence rates than clipping for aneurysms that can be treated with either technique. Ideally, ruptured cerebral aneurysms should be treated at institutions that offer both clipping and coil embolization, and the choice of treatment should be based on a comprehensive assessment of the patient's age; the severity, location, size and shape of the aneurysm; the clipping and coil embolization techniques of the treating physician; and the wishes of the patient and family.

Transient cardiac electrophysiological changes in a rat model of subarachnoid haemorrhage: a brain-heart interaction.

Subarachnoid haemorrhage (SAH) is one of the causes of sudden cardiac death (SCD). However, the time course of ventricular arrhythmias and potential mechanisms responsible for this effect after SAH remain unknown. This study aims to investigate the effect of SAH on ventricular electrophysiological changes and its potential mechanisms in long-term phase. We examined the ventricular electrophysiological remodelling and potential mechanisms in a Sprague Dawley rat model of SAH at six time points (baseline, and Days 1, 3, 7, 14 and 28) and explored the potential mechanisms. We measured the ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT) and left stellate ganglion (LSG) activity at different time points before and after SAH. We also detected neuropeptide Y (NPY) levels in plasma and myocardial tissues by enzyme-linked immunosorbent assay, and quantified NPY 1 receptor (NPY1R) protein and mRNA expression levels by western blotting and quantitative real-time reverse transcription-polymerase chain reaction, respectively. Subarachnoid haemorrhage gradually prolonged QTc intervals, shortened ventricular ERP and reduced VFT during the acute phase, peaking at Day 3. However, no significant changes were observed from Days 14 to 28 compared to Day 0. Subarachnoid haemorrhage gradually increased LSG activity, increased NPY concentrations and up-regulated NPY1R expression in the acute phase of SAH, peaking at Day 3. However, no significant variations were found from Days 14 to 28 compared to Day 0. Subarachnoid haemorrhage increases the transient susceptibility of VAs in the acute phase, and the underlying mechanisms for this response included increased sympathetic activity and up-regulated NPY1R expression.

Correlation between clinical severity and extent of autonomic cardiovascular impairment in the acute phase of subarachnoid hemorrhage

Background and aimTo assess associations between clinical severity and possible dysfunction of autonomic cardiovascular modulation within the acute phase after spontaneous subarachnoid hemorrhage (SAH).MethodsIn this prospective observational study, in 51 patients with spontaneous SAH, Hunt-and-Hess scores (H&H) were assessed and cardiovascular autonomic modulation was monitored within 24 h after SAH-onset. From 5 min time-series of R–R-intervals (RRI) and blood-pressure (BP) recordings, we calculated autonomic parameters including time-domain [RRI-coefficient-of-variation (RRI-CV) and square-root-of-the-mean-squared-differences-of-successive-RRIs (RMSSD)] and frequency-domain parameters [low- and high-frequency-powers of RRI- and BP-modulation (RRI-LF-, RRI-HF-, SBP-LF-powers) and RRI-total-powers]. Data were compared to those of 20 healthy volunteers.ResultsRRI- and BP-values did not differ between groups. Yet, parameters of sympathetic (RRI-LF-powers 141.0 (18.9–402.4) ms2 vs 442.3 (246.8–921.2) ms2, p = 0.001) and total autonomic modulation (RRI-CV 2.4 (1.2–3.7) ms2 vs 3.7 (3.1–5.3) ms2, p = 0.001) were significantly lower in patients than in controls. Subgroup analyses (patients with H&H < 3 vs H&H ≥ 3) and Spearman-rank-correlations revealed increasing loss of sympathetic (RRI-LF-powers 338.6 (179.7–710.4) ms2 vs 72.1 (10.1–175.9) ms2, p = 0.001, rho = − 0.524) and total autonomic modulation (RRI-CV 3.5 (2.3–5.4) ms2 vs 1.6 (1.0–2.8) ms2, p < 0.001, rho = − 0.519) with higher H&H-scores. Multiple-logistic-regression underlined the significant influence of H&H-scores on sympathetic (RRI-LF-powers, p = 0.033) and total autonomic modulation (RRI-CV, p = 0.040) compared to possible confounders (e.g., age, intubation).ConclusionWithin the acute phase, spontaneous SAH induces a decrease in sympathetic and total autonomic cardiovascular modulation. Higher H&H-scores were associated with increasing autonomic dysfunction and may therefore augment the risk of cardiovascular complications and poor clinical outcome.

Spatiotemporal Patterns of Spreading Depolarization and its Correlation with Brain Injury During the Acute Stage of Subarachnoid Hemorrhage in Mice

ObjectiveSpreading depolarization (SD) has been regarded as one cause of neuronal injury in subarachnoid hemorrhage (SAH). However, SD in the hyperacute phase of SAH is still unclear. The objective of this study was to detect real-time spatial-temporal patterns of SD, assess the effect of SD on cerebral blood flow, and test the relationship between SD and brain injury in the acute phase of SAH. MethodsTwenty-eight mice were separated into two groups: 16 animals in the SAH group and 12 animals in the sham group. Experimental SAH was done with an endovascular filament perforation model. Changes in optical reflection were registered with intrinsic optical signal imaging (IOSI) after SAH. Spatial-temporal patterns of SDs were analyzed and brain injury including brain edema and infarction was tested. ResultsTotally, 117 SDs occurred after SAH. According to the hemodynamic response and duration, SDs could be classified into Type I (short SD), Type II (intermediate SD), and Type III (persistent SD). Most of SDs originated from the somatosensory and visual cortex. SDs demonstrated distinct spreading patterns. Moreover, the number and duration of SDs associated with brain water content (p < 0.05, p < 0.01). SDs, especially, persistent SDs associated with infarct volume in the hyperacute phase of SAH (p < 0.001, p < 0.001). ConclusionOur results suggest that SD occurs with a high incidence during the acute stage of SAH in mice. And the lissencephalic mouse brain is capable of different SD propagation patterns. Additionally, SD may aggravate brain edema and induce brain infarction, contributing to early brain injury after SAH.

Modified balloon-assisted coiling instead of acute stenting in the treatment of ruptured wide necked intracranial aneurysms.

The aim of this study was to investigate the safety and efficiency of the modified balloon assisted coiling (mBAC) technique in endovascular treatment (EVT) of ruptured wide-necked aneurysms (WNAs) to avoid stent placement in the acute phase of subarachnoid hemorrhage (SAH). The local neurointerventional radiology database was retrospectively reviewed to identify patients who underwent EVT due to ruptured WNAs by the authors. According to the EVT technique performed, the study sample was divided into 3 groups: conventional BAC, stent assisted coiling (SAC), and mBAC. The patient demographics, aneurysm features, technical and clinical complications, aneurysm occlusion grades, morbidity, and mortality rates were comparatively analyzed. This study involved a total of 113 patients who had ruptured WNAs. The mBAC technique was performed on 26 aneurysms (23 saccular and 3 fusiform) in 26 patients to avoid acute phase stenting. The mean continuous balloon inflation time was 7.1 ± 2.12 min. The initial and follow-up angiographic and clinical outcomes were better in the mBAC group than in the SAC group (p < 0.05). The mBAC technique offers a prolonged, continuous balloon inflation time during the whole coiling process in the treatment of ruptured WNAs. The mBAC technique has the potential to obviate the need for SAC in patients who are candidates for stenting during the acute phase of SAH, and it might be considered a safe and effective endovascular approach with low complication rates and good angiographic and clinical outcomes.

Intra-arterial Contrast-enhanced Micro-computed Tomography Can Evaluate Intracranial Status in the Ultra-early Phase of Experimental Subarachnoid Hemorrhage in Rats

The endovascular perforation (EP) model is a common technique for experimental subarachnoid hemorrhage (SAH) in rats, simulating the pathophysiological features observed in the acute phase of SAH. Due to the drawbacks of large variations in the amount of bleeding, the results obtained from this model require severity evaluation. However, no less-invasive procedure could confirm the precise intracranial conditions immediately after establishing the rat EP model. We created a novel method for evaluating SAH immediately after establishing the rat EP model using intra-arterial contrast-enhanced micro-computed tomography (CT). We administered contrast agents continuously via the carotid artery during surgery and performed CT examination immediately after SAH induction. First, bleeding severity was classified by establishing a scoring system based on the CT findings (cSAH scoring system). Subsequently, we determined the actual SAH distribution macroscopically and histologically and compared it with the cSAH scores. Second, we investigated the contrast agent’s neurotoxicity in rats. Finally, we confirmed the correlation between cSAH scores and SAH severity, including neurological status, cerebral vasospasm, and hematoma volume 24 hr after SAH. Intra-arterial contrast-enhanced micro-CT could visualize the distribution of SAH proportionally to the bleeding severity immediately after establishing the EP model. Moreover, the contrast agent administration was determined not to be neurotoxic to rats. The cSAH scoring revealed a significant correlation with the SAH severity in the rat EP model (P <0.01). Thus, our minimally invasive method provided precise information on intracranial status in the ultra-early phase of SAH in rats EP model.

Mesenchymal stem cell-derived extracellular vesicles promote microglial M2 polarization after subarachnoid hemorrhage in rats and involve the AMPK/NF-κB signaling pathway

Subarachnoid hemorrhage (SAH) is an acute and severe disease with high disability and mortality. Inflammatory reactions have been proven to occur throughout SAH. Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) have shown broad potential for the treatment of brain dysfunction and neuroprotective effects through neurogenesis and angiogenesis after stroke. However, the mechanisms of EVs in neuroinflammation during the acute phase of SAH are not well known. Our present study was designed to investigate the effects of MSCs-EVs on neuroinflammation and the polarization regulation of microglia to the M2 phenotype and related signaling pathways after SAH in rats. The SAH model was induced by an improved method of intravascular perforation, and MSCs-EVs were injected via the tail vein. Post-SAH assessments included neurobehavioral tests as well as brain water content, immunohistochemistry, PCR and Western blot analyses. Our results showed that MSCs-EVs alleviated the expression of inflammatory cytokines in the parietal cortex and hippocampus 24 h and 48 h after SAH and that MSCs-EVs inhibited NF-κB and activated AMPK to reduce inflammation after SAH. Furthermore, MSC-EVs regulated the polarization of microglia toward the M2 phenotype by downregulating interleukin-1β, cluster of differentiation 16, cluster of differentiation 11b, and inducible nitric oxide synthase and upregulating the expression of cluster of differentiation 206 and arginase-1. Additionally, MSCs-EVs inhibited the neuroinflammatory response and had neuroprotective effects in the brain tissues of rats after SAH. This study may support their use as a potential treatment strategy for early SAH in the future.

Cerebral nitric oxide and mitochondrial function in patients suffering aneurysmal subarachnoid hemorrhage\u2014a translational approach

BackgroundCerebral ischemia and neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) are major contributors to poor neurological outcome. Our study set out to investigate in an exploratory approach the interaction between NO and energy metabolism following SAH as both hypoxia and inflammation are known to affect nitric oxide (NO) metabolism and NO in turn affects mitochondria.MethodsIn seven patients under continuous multimodality neuromonitoring suffering poor-grade aneurysmal SAH, cerebral metabolism and NO levels (determined as a sum of nitrite plus nitrate) were determined in cerebral microdialysate for 14 days following SAH. In additional ex vivo experiments, rat cortex homogenate was subjected to the NO concentrations determined in SAH patients to test whether these NO concentrations impair mitochondrial function (determined by means of high-resolution respirometry).ResultsNO levels showed biphasic kinetics with drastically increased levels during the first 7 days (74.5 ± 29.9 μM) and significantly lower levels thereafter (47.5 ± 18.7 μM; p = 0.02). Only during the first 7 days, NO levels showed a strong negative correlation with brain tissue oxygen tension (r = − 0.78; p < 0.001) and a positive correlation with cerebral lactate (r = 0.79; p < 0.001), pyruvate (r = 0.68; p < 0.001), glutamate (r = 0.65; p < 0.001), as well as the lactate-pyruvate ratio (r = 0.48; p = 0.01), suggesting mitochondrial dysfunction. Ex vivo experiments confirmed that the increase in NO levels determined in patients during the acute phase is sufficient to impair mitochondrial function (p < 0.001). Mitochondrial respiration was inhibited irrespectively of whether glutamate (substrate of complex I) or succinate (substrate of complex II) was used as mitochondrial substrate suggesting the inhibition of mitochondrial complex IV. The latter was confirmed by direct determination of complex IV activity.ConclusionsExploratory analysis of our data suggests that during the acute phase of SAH, NO plays a key role in the neuronal damage impairing mitochondrial function and facilitating accumulation of mitochondrial substrate; further studies are required to understand mechanisms underlying this observation.

Morphological Characteristics of Neuronal Death After Experimental Subarachnoid Hemorrhage in Mice Using Double Immunoenzymatic Technique.

Subarachnoid hemorrhage (SAH) is a devastating disease. Neuronal death is an important pathophysiology in the acute phase of SAH, but the histopathological features of dying neurons have been poorly studied. Using several staining methods including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and microtubule-associated protein 2 (MAP-2) double immunolabeling, we investigated the morphological changes of nucleus and cytoskeleton in neurons and sought susceptible areas to neuronal death in filament perforation SAH mice under light microscope. TUNEL and MAP-2 double immunolabeling clearly showed morphological features of shrunken cytoplasm and sometimes curl-like fibers in dying neurons, besides nuclear abnormalities. More dying neurons were detected in the moderate SAH group than in the mild SAH group, and the temporal base cortex was the most susceptible area to neuronal death with deoxyribonucleic acid (DNA) damage among the cerebral cortices and hippocampus at 24 hr after SAH (p<0.01, ANOVA). Lesser hippocampal neuronal death was observed at 24 hr, but neuronal death was significantly increased in the CA1 region at 7 days after SAH (p<0.05, unpaired t-test). Using TUNEL and MAP-2 double immunolabeling, morphological features of not only the nucleus but also the cytoplasm in post-SAH neuronal death with DNA damage can be observed in detail under light microscope.

Spreading Depolarization during the Acute Stage of Experimental Subarachnoid Hemorrhage in Mice.

Spreading depolarization (SD) has been suggested as a pathomechanism for delayed cerebral ischemia after subarachnoid hemorrhage (SAH). However, the role of SD during the acute phase of SAH is still unclear. The objective of this study was to investigate (a) the occurrence of SD with intrinsic optical signal (IOS) imaging, (b) the effect of ketamine on SD, and (c) the resulting brain edema (brain water content (BWC)) during the acute stage of experimental SAH in mice. SAH was elicited by the endovascular filament perforation method. After SAH or sham operation, ketamine or saline, 30mg/kg, was given every half hour. Changes in tissue light reflectance were recorded with IOS. BWC was measured during the acute stage. Overall, 199 SDs occurred in SAH groups and 33 SDs appeared in sham groups. These SDs displayed distinct originating and spreading patterns. Compared with saline, ketamine decreased SD spread and influenced the amplitude, duration, and speed of SD. However, the occurrence of SD was not prevented by ketamine. Moreover, ketamine did not reduce BWC after SAH. These results demonstrate that SD occurs with a high incidence during the acute stage of SAH. SDs are heterogeneous in incidence, origination, and propagation. It remains unclear whether ketamine effects on SD may be viewed as therapeutically beneficial after SAH.

Early Antiinflammatory Therapy Attenuates Brain Damage After Sah in Rats.

BackgroundEarly inflammatory processes may play an important role in the development of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experimental studies suggest that anti-inflammatory and membrane-stabilizing drugs might have beneficial effects, although the underlying mechanisms are not fully understood. The aim of this study was to investigate the effect of early treatment with methylprednisolone and minocycline on cerebral perfusion and EBI after experimental SAH.MethodsMale Sprague-Dawley rats were subjected to SAH using the endovascular filament model. 30 minutes after SAH, they were randomly assigned to receive an intravenous injection of methylprednisolone (16mg/kg body weight, n=10), minocycline (45mg/kg body weight, n=10) or saline (n=11). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (LCBF) over both hemispheres were recorded continuously for three hours following SAH. Neurological assessment was performed after 24 hours. Hippocampal damage was analyzed by immunohistochemical staining (caspase 3).ResultsTreatment with methylprednisolone or minocycline did not result in a significant improvement of MABP, ICP or LCBF. Animals of both treatment groups showed a non-significant trend to better neurological recovery compared to animals of the control group. Mortality was reduced and hippocampal damage significantly attenuated in both methylprednisolone and minocycline treated animals.ConclusionThe results of this study suggest that inflammatory processes may play an important role in the pathophysiology of EBI after SAH. Early treatment with the anti-inflammatory drugs methylprednisolone or minocycline in the acute phase of SAH has the potential to reduce brain damage and exert a neuroprotective effect.

Preoperative Three-Dimensional Angiography May Reduce Ischemic Complications During Clipping of Ruptured Intracranial Aneurysms

Microsurgical clipping of aneurysms demands precise spatial understanding of aneurysm morphology and vascular geometry. We analyzed the impact of preoperative three-dimensional (3D) angiographic imaging on clinical and angiographic outcome after clipping of ruptured intracranial aneurysms. This is a retrospective analysis of consecutive patients who underwent microsurgical clipping during the acute phase of subarachnoid hemorrhage between 2010 and 2017. Surgical planning was made based on two-dimensional (2D) or 3D angiographic images. We retrospectively compared complication rates, morbidity, and angiographic outcome between these 2 groups. A total of 157 patients (mean age: 54.8 ± 13.1 years) were included in the study. Preoperative 3D angiographic imaging was available for 117 cases. The rate of procedure-related ischemia was significantly lower in the 3D group (16.2%) than in the 2D group (35.0%; P= 0.013). In the multivariate analysis, 2D imaging alone remained as independent factor for subsequent brain ischemia (odds ratio: 2.8, 95% confidence interval 1.2-6.6; P= 0.018). Favorable outcome (modified Rankin scale ≤2) was more often attained in the 3D group (70.0%) than in the 2D group (41.9%; P= 0.002). The rate of complete aneurysm occlusion was not significantly different between the 2 groups (P= 0.967). In our study, accurate operation planning using 3D angiography was associated with a lower ischemic complication rate after clipping of ruptured intracranial aneurysms, which may potentially influence clinical outcome.

Stent-assisted treatment of ruptured intracranial aneurysms in the acute phase: A single center experience.

IntroductionThe purpose of this study was to analyze the results of patients with ruptured aneurysms who were treated with a specific microstent in the acute phase of subarachnoid hemorrhage.MethodsData from patients with acutely-ruptured intracranial aneurysm treated with the Neuroform stent in the period between 2003 and 2016 were retrospectively assessed, addressing aneurysm occlusion and clinical outcome with a focus on periprocedural complications.ResultsTwenty-nine consecutive patients with ruptured intracranial aneurysms were included in the analysis. Periprocedural hemorrhagic complications were stated in six patients, leading to death in four. Thromboembolic complications were observed in seven patients, among whom only one affected the clinical outcome with death due to basilar thrombosis. Immediate complete occlusion and occlusion with residual neck was achieved in 79.3% of cases.ConclusionStent-assisted coiling of acutely-ruptured aneurysms achieves good immediate aneurysm occlusion. Rates of intra- and periprocedural adverse events observed in this series were significant, but did not translate to corresponding morbidity and mortality in all cases. The retrospective analysis did not allow assessing the overall risks of endovascular therapy with stent use in ruptured and complex aneurysm when compared to the overall risks with other alternative options.

Abstract TP400: Acute Catecholamine Surge Reflects the Prognosis in Patients With Aneurysmal Subarachnoid Hemorrhage

Objective: We investigated that the characteristics of serum catecholamine concentration at the hyper-acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship between patient outcome and delayed vasospasm. Methods: Patients with aneurysmal SAH (n=170) were prospectively enrolled between 2008 and 2011. Baseline demographic data and physiological parameters, including plasma concentrations of adrenaline (AD), noradrenaline (NA) and dopamine (DP) were evaluated. Results: On admission, plasma AD, NA and DP levels were significantly higher in patients with a poor clinical grade on admission (Hunt and Kosnik: IV-V), compared to those with a good clinical grade on admission (Hunt and Kosnik: I-III). AD showed a significantly high concentration immediately after the onset of SAH and then rapidly decreased. The levels of NA peaked within 6 hours after onset, then significantly decreased. The time course of the elevation of DP showed a similar trend to that of NA. The each catecholamine levels significantly correlated with each other. Multivariate analyses demonstrated age, poor clinical grade, plasma AD and NA levels were predictors of poor patient outcome. Poor clinical grade, Fisher scale and plasma AD level were predictors of the development of delayed vasospasm. Conclusion: The present study suggests that sympathetic activation in patients in the acute phase of SAH reflects the severity of SAH, and is closely related to the development of delayed vasospasm, leading to the subsequent immune response and inflammatory reactions. Suppressing catecholamine surge in hyper-acute phase may contribute to prevention of vasospasm and improvement of patient outcome.

Abstract WP386: Acute Catecholamine Surge in Patients with Aneurysmal Subarachnoid Hemorrhage: Characteristics and Prognostic Value

Objectives: The characteristics of serum catecholamine concentration at the hyper-acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship between patient outcome and delayed vasospasm were investigated. Methods: Patients with aneurysmal SAH (170) were prospectively studied between August 2008 and June 2011. Baseline demographic data and physiological parameters, including plasma concentrations of adrenaline (AD), noradrenaline (NA) and dopamine (DP) were evaluated for all patients. Results: On admission, plasma AD, NA and DP levels were significantly higher in patients with a poor clinical grade on admission (Hunt &amp; Kosnik: IV-V), compared to those with a good clinical grade on admission (Hunt &amp; Kosnik: I-III). AD showed a markedly high concentration immediately after the onset of SAH and then rapidly decreased. NA levels peaked within 6 hours after onset, then significantly decreased. The increase of DP with time was not significant, but showed a similar trend to that of NA. The level of each catecholamine showed significant mutual correlation. Multivariate analyses demonstrated age, poor clinical grade, plasma AD and NA levels were predictors of poor patient outcome, and.poor clinical grade, Fisher scale and plasma AD level were predictors of the development of delayed vasospasm. Conclusions: The present findings suggest that sympathetic activation in patients in the acute phase of SAH reflects the severity of SAH, and is closely related to the development of delayed vasospasm, leading to the subsequent immune response and inflammatory reactions. Strategies for suppressing catecholamine at the hyperacute phase may contribute to vasospasm prevention and improve patient outcome.

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

OBJECTIVE Although cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH. METHODS Twenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites. RESULTS Changes in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P50) was estimated to be 22.4 minutes (95% confidence intervals 17.0-30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after initiation of SAH. On NADH fluorescence images CSD was initially observed in the anterior cortex; it propagated through the entire hemisphere in the direction of the occipital cortex at a rate of 3 mm/minute, with repolarization in 2.3 ± 1.2 minutes. DC potential recording sites that had undergone CSD were found to have intact tissue 24 hours later. Compared with depolarization that caused 50% neuronal damage, the duration of CSD was too short to cause histological damage. CONCLUSIONS CSD was successfully visualized using NADH fluorescence. It propagated from the anterior to the posterior cortex along with an increase in CBF. The duration of depolarization in CSD (2.3 ± 1.2 minutes) was far shorter than that causing 50% neuronal damage (22.4 minutes) and was not associated with histological damage in the current experimental setting.

Evolution of diffusion tensor imaging parameters after acute subarachnoid haemorrhage: a prospective cohort study.

Few studies assessed diffusion tensor imaging (DTI) changes in the acute phase of subarachnoid haemorrhage (SAH). We prospectively evaluated DTI parameters in the acute phase of SAH and 8-10days after and analysed whether changes could be related to SAH severity or to the development of delayed cerebral ischemia (DCI). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) changes over time were assessed in a prospective cohort of patients with acute SAH. Two MRI studies were performed at <72h (MRI-1) and 8-10days (MRI-2). DTI parameters were recorded in 15 ROIs. Linear mixed regression models were used. Forty-two patients were included. Subtle changes in DTI parameters were found between MRI-1 and MRI-2. At the posterior limb of internal capsule (PLIC), a weak evidence of a 0.02 mean increase in FA (p=0.064) and a 17.55×10-6mm2/s decrease in ADC (p=0.052) were found in MRI-2. Both FA and ADC changed over time at the cerebellum (increase of 0.03; p=0.017; decrease of 34.73×10-6mm2/s; p=0.002, respectively). Patients with DCI had lower FA values on MRI-1 and lower ADC on MRI-2, although not reaching statistical significance, compared to non-DCI patients. DTI parameters on MRI-1 were not correlated to clinical admission scales. ADC and FA values show subtle changes over time in acute SAH at the PLIC and cerebellum although not statistically associated with the severity of SAH or the occurrence of DCI. However, DTI changes occurred mainly in DCI patients, suggesting a possible role of DTI as a marker of DCI.