Endovascular treatment for cerebral vasospasm following aneurysmal subarachnoid hemorrhage: predictors of outcome and retreatment.

OBJECTIVE: Although endovascular therapy has been widely adopted for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), its effect on clinical outcomes remains incompletely understood. The aims of this retrospective cohort study are to evaluate the outcomes of endovascular intervention for post-aSAH vasospasm and identify predictors of functional independence at discharge and repeat endovascular vasospasm treatment. METHODS: We assessed the baseline and outcomes data for patients with aSAH who underwent endovascular vasospasm treatment at our institution, including intra-arterial (IA) vasodilator infusion and angioplasty. Statistical analyses were performed to determine factors associated with good outcome at discharge (modified Rankin Scale 0-2) and repeat endovascular vasospasm treatment. RESULTS: The study cohort comprised 159 patients with a mean age of 52 years. Good outcome was achieved in 17% of patients at discharge (26/150 patients), with an in-hospital mortality rate of 22% (33/150 patients). In the multivariate analysis, age (OR 0.895; p=0.009) and positive smoking status (OR 0.206; p=0.040) were negative independent predictors of good outcome. Endovascular retreatment was performed in 34% (53/156 patients). In the multivariate analysis, older age (OR 0.950; p=0.004), symptomatic vasospasm (OR 0.441; p=0.046), initial treatment with angioplasty alone (OR 0.096; p=0.039), and initial treatment with combined IA vasodilator infusion and angioplasty (OR 0.342; p=0.026) were negative independent predictors of retreatment. CONCLUSION: We found a modest rate of functional independence at discharge in patients with aSAH who underwent endovascular vasospasm treatment. Older patients and smokers had worse functional outcomes at discharge. Initial use of angioplasty appears to decrease the need for subsequent retreatment.

Application of lumbar drainage in vasospasm after spontaneous subarachnoid hemorrhage and prevention of late cerebral infarction.

Cerebral vasospasm, especially delayed cerebral ischemia following subarachnoid hemorrhage (SAH) is the most important complication that effects mortality and morbidity of patients with intracranial aneurysms. The presence of cerebral vasospasm has been correlated with an increase in mortality in the first 2 weeks after SAH. Despite clinical studies and research, the etiopathogenesis of cerebral vasospasm is not understood exactly and there is not yet an effective therapy. The aim of our study was to investigate the effect of application of lumber drainage on vasospasm and delayed cerebral infarction following SAH and to examine the incidence of complications. Patient groups were determined by retrospective screening of 70 patients who underwent a surgical operation at the Osmangazi University Medical Faculty Department of Neurosurgery between 2009 and 2013 after a diagnosis of ruptured aneurysmal SAH. After the application of lumbar drainage, the complications and mortality after aneurysm surgery was significantly decreased and correlated with the amount of hemorrhagic cerebrospinal fluid drainage.

Clinical worsening in reversible cerebral vasoconstriction syndrome.

IMPORTANCE: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches and evidence of vasoconstriction with subsequent resolution. The clinical course of RCVS is traditionally considered monophasic and benign. However, recurrent episodes of focal neurological symptoms have been described after initial presentation. OBJECTIVE: To define the frequency, timing, and consequences of clinical worsening in patients with diagnosis of RCVS. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study of consecutive patients with RCVS at 2 referral institutions for neurological disease. MAIN OUTCOME AND MEASURE: Clinical worsening after diagnosis of RCVS. We defined clinical worsening as new permanent or transient neurological deficits (compared with presenting signs and symptoms) or new onset of seizures. We performed a logistic regression analysis to assess associations between patient characteristics and clinical worsening. Functional outcome was assessed at 1 to 3 months using the modified Rankin score. RESULTS: We identified 59 patients (median age, 47 years; interquartile range, 32-54 years) with RCVS. Twenty patients (34%) experienced clinical worsening after a median of 2.5 days (range, several hours to 14 days). Eight of the 20 patients who worsened had permanent deficits, including 4 who died. We did not find an association between age, sex, smoking, migraine, acute or chronic hypertension, peripartum state, or use of serotonergic drugs with clinical worsening. Clinical worsening was associated with radiological infarction (P = .001) and worse functional outcome (P < .004). Functional outcome was favorable (modified Rankin score 0-2) in 51 patients (86.4%). CONCLUSIONS AND RELEVANCE: Clinical worsening after diagnosis is common in patients with RCVS. Thus, RCVS is self-limited but not strictly monophasic. Most patients have a very favorable outcome, but clinical worsening may result in permanent deficits.

Clinical characteristics and outcomes of neurogenic stress cadiomyopathy in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an often devastating form of stroke. Aside from the initial hemorrhage, cardiac complications can occur resulting in neurogenic stress cardiomyopathy (NCM), leading to impaired cardiac function. We investigated whether aSAH patients with NCM had poorer long term functional outcomes than patients without NCM. Mortality, vasospasm, and delayed ischemic complications were also evaluated. METHODS: A retrospective study of all patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) from January 2006 to June 2011 (n=299) was conducted. Those patients who underwent an echocardiogram were identified (n=120) and were assigned to the NCM (n=49) category based on echocardiographic findings defined by a depressed ejection fraction (EF%) along with a regional wall motion abnormality (RWMA) in a non-vascular pattern. Primary outcome measures included in-hospital mortality and functional outcomes as measured by the Modified Barthel Index (mBI) at 3 months and one year. Secondary analysis determined if there was an association between NCM, cerebral vasospasm and delayed cerebral ischemia. RESULTS: 16% of aSAH patients developed NCM. Mortality was higher (p<.001) in the NCM group (n=23[46.9%]) than in the non-CM group (n=28[11.2%]). Patients with NCM had poorer functional outcomes as measured by the mBI at both 3 months (p=.002) and 12 months (p=.014). The Hunt-Hess score was predictive of functional outcome as measured by the mBI at both 3 months (p=.002) as well as at 1 year (p=.014). NCM was associated with both death (p=.047 CI, 1.012-7.288) and vasospasm (p=.008 CI, 1.34-6.66) after correction for Hunt-Hess grade. Tobacco use (p<.001) and a history of diabetes mellitus (p<.009) were also associated with vasospasm. NCM was associated with higher in-hospital mortality (p=.047) in multivariate analysis. CONCLUSION: NCM is seen in a substantial number of aSAH patients and when present, it is associated with higher mortality and poorer long-term functional outcomes. This finding may guide further prospective studies in order to determine if early recognition of NCM as well as optimization of cardiac output would improve mortality.

Endovascular treatment: balloon angioplasty versus nimodipine intra-arterial for medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) accounts significant morbimortality after aneurysmal subarachnoid hemorrhage. The objective of this study was to compare the clinical outcome of patients with CV treated by 2 endovascular procedures: intra-arterial nimodipine angioplasty (IANA) and balloon angioplasty (BA). Between 2008 and June 2011, we performed 22 IANA and 8 BA in 30 patients. The mean age was 44 years and 60% was female. In 17 patients, the treatment was clipping, whereas 13 underwent coil treatment. The CV was severe in 63%, moderate in 30%, and mild in 7%. Good outcome between 2 groups was similar (P = .36). The clinical outcome according to the subgroups of CV severity and modality treatment was equivalent (P = .22). Mortality at 3 months was 16% and 20% at 1 year. We did not find differences in the clinical outcome despite the fact that both techniques produce adequate angiographic resolution of CV.

Hyperacute cerebral aneurysm rerupture during CT angiography.

OBJECT: The object of this study was to identify the clinical features and outcomes of a subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) who had active contrast extravasation from a ruptured aneurysm during initial cerebral CT angiography (CTA). METHODS: The authors performed a retrospective study of spontaneous SAH cases involving patients treated at their institute. They identified 9 cases in which active contrast extravasation was evident on the initial CT angiogram. Another 12 similar cases were also identified in a literature review and data was gathered from these cases to evaluate the outcomes. RESULTS: Analysis of all 21 cases revealed that the overall outcomes in cases characterized by active aneurysmal bleeding during CTA were poor. Seventy-six percent of patients had unfavorable results. Patients who showed poor neurological status at presentation died no matter what kind of treatment they received. In contrast, patients who presented with good neurological status initially had a chance of favorable outcome. Among the patients with good initial neurological status, most demonstrated rapid deterioration of their condition during the CTA examination; only those who received immediate and effective decompressive surgery and aneurysm obliteration had good results. CONCLUSIONS: Active aneurysmal rebleeding during CTA is an uncommon but devastating event. Though the mortality of this distinct group of patients remains high, a clinical subgroup may benefit from immediate surgery. Patients with good initial neurological status who show rapid neurological deterioration may still have a favorable outcome if they undergo timely and successful decompressive surgery and proper aneurysm obliteration. Patients who present with poor neurological status do badly, and there is no effective treatment for such patients.

Early surgery of multiple versus single aneurysms after subarachnoid hemorrhage: an increased risk for cerebral vasospasm?

OBJECT: As many as 33% of patients suffering from subarachnoid hemorrhage (SAH) present with multiple intracranial aneurysms (MIAs). It is believed that aneurysm surgery has the potential to increase the risk of cerebral vasospasm due to surgical manipulations of the parent vessels and brain tissue. Consequently, 1-stage surgery of MIAs, which usually takes longer and requires more manipulation, could even further increase the risk of vasospasm. The aim of this study is to define the correlation between vasospasm and the operative treatment of single intracranial aneurysms versus MIAs in a 1-stage operation. METHODS: The authors analyzed a database including 1016 patients with SAH, identified retrospectively between 1989 and 1996 and prospectively collected between 1997 and 2004. Exclusion criteria were endovascular treatment, surgery after SAH Day 3, and, in patients with MIAs, undergoing more than 1 operation. Cerebral vasospasm was diagnosed by transcranial Doppler (TCD) ultrasonography and was defined as a maximum mean blood flow velocity > 120 cm/second. The diagnosis of symptomatic vasospasm was made if a new neurological deficit occurred that could not be explained by concomitant complications. RESULTS: A total of 643 patients who experienced 810 aneurysms were included. Four hundred twenty-four patients were female (65.9%) and 219 were male (34.1%) with an average age of 53.1 years. One hundred twenty-one patients (18.8%) were diagnosed with MIAs. Maximum mean flow velocities measured by TCD were 131 cm/second in patients with MIAs and 129.5 cm/second in patients with single intracranial aneurysms. The incidence of TCD vasospasm (p = 0.561) as well as of symptomatic vasospasm (p = 0.241) was not significantly different in the 2 groups. CONCLUSIONS: Clipping of more than 1 aneurysm in a 1-stage operation within 72 hours after SAH can be performed without increasing the risk of cerebral (TCD) vasospasm and symptomatic vasospasm.

Transdermal nicotine replacement therapy in cigarette smokers with acute subarachnoid hemorrhage.

BACKGROUND: We evaluated the safety of nicotine replacement therapy (NRT) in active smokers with acute (aneurysmal) subarachnoid hemorrhage (SAH). METHODS: A retrospective observational cohort study was conducted in a prospectively collected database including all SAH patients admitted to an 18-bed neuro-ICU between January 1, 2001 and October 1, 2007. Univariate and multivariable models were constructed, employing stepwise logistic regression. The primary endpoint was 3-month mortality. Delayed cerebral ischemia (DCI) due to vasospasm, angiographic and TCD evidence of vasospasm, and delirium were secondary endpoints. RESULTS: Active cigarette smokers admitted with SAH included 128 that received NRT and 106 that did not. Patients were well-matched for age, admission Hunt-Hess Grade, radiographic findings, and APACHE II scores, but those who received NRT were more likely to be heavy smokers (>10 cigarettes daily), diabetic, heavy alcohol users, and to have cerebral edema on admission. NRT was associated in multivariate analysis with a lower risk of death at 3 months (OR 0.12, 95% CI 0.04-0.37, P < 0.001). There were no differences in the frequency of DCI and most other medical complications, but delirium (19 vs. 9%, P = 0.006) and seizures (9 vs. 2%, P = 0.024) were more common in patients who received NRT. CONCLUSIONS: Despite vasoactive properties, administration of NRT among active smokers with acute SAH appeared to be safe, with similar rates of vasospasm and DCI, and a slightly higher rate of seizures. The association of NRT with lower mortality could be due to chance, to uncontrolled factors, or to a neuroprotective effect of nicotine in active smokers hospitalized with SAH, and should be tested prospectively.

Comparison of intrathecal dotarizine and nimodipine treatments in cerebral vasospasm after subarachnoid hemorrhage: an experimental study in rabbits.

BACKGROUND: cerebral vasospasm (CVS) is one of the most considerable complications of subarachnoid hemorrhage (SAH). The aim of this study was to assess and to compare the ability of intrathecal dotarizine and nimodipine to prevent and treat vasospasm in a rabbit model of subarachnoid hemorrhage. METHOD: thirty male New Zealand white rabbits weighing 2,500-3,000 g were allocated into five groups randomly. The treatment groups were as follows: Control, only SAH, SAH/Dotarizine, SAH/Nimodipine, SAH/Vehicle. Forty-eight hours after SAH injection, all animals underwent femoral artery catheterization procedure by open surgery under anesthesia and angiography performed for each animal in the fifth day just before sacrifice. FINDINGS: basilar artery vessel diameters are measured by angiography. Basilar artery vessel diameters and luminal sectional areas are measured in pathology slides. There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). CONCLUSIONS: these findings demonstrate that calcium channel blocker dotarizine has marked vasodilatory effect in an experimental model of SAH in rabbits. Nimodipine is an effect-proven agent in CVS, but dotarizine may take place of it.

Depresiones corticales propagadas y su posible rol en la fisiopatología del daño neuronal subsecuente a la hemorragia subaracnoidea / Cortical spreading depressions and their role in the pathophysiology of neuronal damage subsequent to aneurysmal subarachnoid hemorrhage

El vasoespasmo cerebral es la principal causa potencialmente tratable de mortalidad e incapacidad en pacientes que sufren hemorragia subaracnoidea aneurismática (HSA). Sin embargo, a la fecha no existe un tratamiento eficaz para el mismo. La reciente demostración de la falta de respuesta clínica a la reversión farmacológica del espasmo arterial a consecuencia de HSA ha obligado un replanteo de los fundamentos fisiopatológicos de los déficits neurológicos isquémicos tardíos (“delayed ischemic neurologic déficit”, DIND) a consecuencia de HSA, los cuales se creían en relación al espasmo arterial observado en pacientes con HSA. Desde la demostración de hallazgos electrocorticográficos de depresión cortical propagada (“cortical spreading depression”, CSD) en pacientes con HSA, un interés creciente se ha despertado respecto del rol de estos fenómenos en la fisiopatología de los DIND observados en pacientes con HSA. Cuando inducidas en un cerebro saludable, las CSD se asocian con un aumento del flujo sanguíneo cerebral, facilitando la entrega del cerebro de los sustratos energéticos necesarios. En un cerebro que ha sido lesionado, sin embargo, la CSD se asocia con una reducción en flujo sanguíneo cerebral, lo cual, en el contexto de un aumento de las necesidades de energía, conduce a la insuficiencia energética y la hipoxia, empeorando así el daño cerebral. Estas observaciones sugieren que el déficit de energía producida por la CSD es un factor clave en la patogénesis de los DIND observados a consecuencia de HSA. Este resumen detalla características sobresalientes de las CSD y su potencial relevancia en la fisiopatología del vasoespasmo.

Cerebral vasospasm is the leading potentially treatable cause of mortality and disability in patients with aneurysmatic subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on delayed ischemic neurologic deficits (DIND) that follow SAH, which were long believed the effect of the arterial spasm observed in patients with SAH. Since the discovery of electrocorticographic cortical spreading depressions (CSD) in patients with SAH, increasing interest has been shown on the role of these phenomena in the pathophysiology of DIND observed in patients with HSA. When induced in a healthy brain, CSD are associated with an increase in cerebral blood flow by facilitating the delivery of the necessary energy substrates. In a brain that has been injured, however, CSD are associated with a reduction in cerebral blood flow, which, in the context of increased energy requirements leads to energy shortage and hypoxia, thus worsening brain damage. These observations suggest that the energetic deficit produced by the CSD is a key factor in the pathogenesis of DIND observed as a result of HSA. This review details striking characteristics of CSD and their potential relevance in the pathophysiology of vasospasm.

Costs of vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To assess the impact of vasospasm on costs, length of stay, and mortality among inpatients with aneurysmal subarachnoid hemorrhage. METHODS: We combined hospital accounting and physician billing data for a consecutive cohort of 198 patients who underwent surgical clipping or endovascular coiling for subarachnoid hemorrhage repair. We considered patients with transcranial Doppler (TCD) velocity of 120 cm/s or greater in the middle cerebral artery to have TCD-defined vasospasm and patients with delayed ischemic neurological deficit to have symptomatic vasospasm. We compared outcomes of patients with TCD-defined vasospasm (n = 116) and those without (n = 73) and patients with symptomatic vasospasm (n = 62) and those without (n = 127), adjusting for demographic and clinical characteristics. RESULTS: In adjusted analyses, the incremental cost attributable to TCD-defined vasospasm was 1.20 times higher (95% confidence interval, 1.06-1.36; P = .004) than for patients without TCD-defined vasospasm. Length of stay was an estimated 1.22 times longer for patients with TCD-defined vasospasm (95% CI, 1.07-1.39; P < .01). For symptomatic vasospasm, adjusted costs were 1.27 times higher (95% CI, 1.12-1.43; P < .001) and length of stay was an estimated 1.24 times longer (95% CI, 1.09-1.40; P < .01) for patients with vasospasm than for those without. There was no significant relationship between either type of vasospasm and in-hospital mortality. CONCLUSION: Patients with subarachnoid hemorrhage and TCD-defined or symptomatic vasospasm incur higher inpatient costs and longer hospital stays than those without vasospasm.

Neuroanesthesiology update.

Recent literature contains many reports of value to clinicians providing anesthetic or intensive care for neurosurgical patients or patients experiencing, or at risk for, neurological impairment. We will review many of these articles, focusing on those that address intracranial hemorrhage, intracranial procedures, carotid endarterectomy, spine surgery, and the determinants of outcome in patients with evolving or new-onset neurologic disease. Additionally, we will review articles addressing neurotoxicity, neuroprotection, and nervous system monitoring.

Factors associated with the development of anemia after subarachnoid hemorrhage.

INTRODUCTION: Anemia is common after subarachnoid hemorrhage (SAH) and may exacerbate the reduction in oxygen delivery that underlies delayed cerebral ischemia. Fall in hemoglobin may relate to blood loss as well as inflammatory suppression of erythropoiesis. Identifying factors associated with anemia may facilitate targeted interventions, such as the use of erythropoiesis-stimulating agents, which could minimize the burden of anemia and reduce red blood cell (RBC) transfusion requirements. METHODS: We analyzed a cohort of patients with spontaneous SAH admitted over a 3-year period who survived at least 4 days. All patients had daily hematocrit values drawn while in the ICU. Multivariate regression was performed to determine baseline and early post-admission variables associated with development of anemia (defined as hematocrit < 30%). RESULTS: Anemia developed in 47% of 243 patients with SAH after a mean of 3.5 days (median 2 days). Admission variables independently associated with anemia were female gender (OR 3.7, 95% CI 1.8-7.6), baseline hematocrit < 36% (OR 3.9, 1.5-10.1 compared to 36-45%), history of hypertension (OR 2.1, 1.05-4.2), and poor clinical grade (OR 5.9, 2.3-15.0). Surgical aneurysm treatment (OR 13.5, 6.0-30.3) and greater admission SIRS score (OR 5.7, 1.7-19.2 if 3-4 criteria for systemic inflammatory response syndrome were met on day of admission compared to none) were also associated with fall in hematocrit. CONCLUSIONS: It may be possible to predict those most likely to develop anemia using simple baseline clinical variables. Anemia was strongly related to surgery, likely through greater blood loss, and greater systemic inflammatory response on admission, possibly explained by cytokine-mediated inhibition of RBC production.

Can a "novice" do aneurysm surgery? Surgical outcomes in a low-volume, non-subspecialised neurosurgical unit.

The objective of this paper is to review the results of a junior general neurosurgeon performing aneurysm surgery and compare these to the remainder of his low-volume unit. Prospectively collected data was analysed for 114 aneurysms clipped in 99 patients between July 2001 and May 2005. Overall there was a 0.9% mortality rate and 10.8% complication rate. The favourable outcome rate for the unit was 100% for unruptured aneurysms, 90.4% for grades 1-3 patients and 30% for poor grade patients (grades 4 and 5). The novice neurosurgeon had no mortality and a favourable outcome rate of 94.7% for grades 1-3 patients and 50% for poor grade patients. Acceptable results can be obtained with cerebral aneurysm surgery in a low-volume centre by Australian-trained, non-subspecialty neurosurgeons.

Endovascular embolization vs surgical clipping in treatment of cerebral aneurysms: morbidity and mortality with short-term outcome.

BACKGROUND: Endovascular embolization of cerebral aneurysms has evolved rapidly worldwide within the last years, and has gained more popularity at the expense of surgical clipping; however, both regimens have inherent risks. This study was undertaken to asses the cerebral complications associated with both modalities of cerebral aneurysm treatment. METHODS: We retrospectively reviewed the charts, operative and embolization reports, and imaging of patients who underwent surgical clipping or embolization for cerebral aneurysms at our institution between October 2001 and October 2004. Patients were divided into 2 groups: group A, patients who had confirmed subarachnoid hemorrhage; group B, patients with unruptured cerebral aneurysms. Patients belonging to group A were evaluated according to the Hunt and Hess scale with their computed tomography scan evaluated according to Fisher scale. Short-term outcome was measured with Glasgow Outcome Scale for both groups. RESULTS: One hundred thirty-three patients with 168 aneurysms were treated; 95 (71.4%) were women and 38 (28.6%) men; mean age was 60.28 years. Hypertension (29.6%) was the most commonly encountered risk factor; average size of aneurysms treated was 7.21 mm; 53 patients belonged to group A. Seven patients were Hunt and Hess grade I, 23 grade II, 11 grade III, 7 grade IV, and 5 grade V. Eighty patients belonged to group B; for both groups, the periprocedural technical complication rate associated with coiling was 8.4% vs 19.35% with clipping. Follow-up angiographic results were better with clipping, as total aneurysm occlusion was 81.4% vs 57.5% with coiling. In group A, the incidence of angiographic vasospasm was 17.4% vs 45.4% with coiling vs clipping, whereas the incidence of shunt-dependant hydrocephalus was comparable with embolization and clipping. In group A, excellent outcome was achieved in 62% vs 44% (endovascular vs surgical) of subgroups, whereas in group B, it was 93% vs 81%, respectively. CONCLUSION: With rapidly evolving technology of endovascular embolization, accumulated experience, and good selection of patients with optimum angioanatomical criteria and endovascular accessibility, our results of morbidity and mortality associated with both modalities of cerebral aneurysm treatment with short-term outcome show that endovascular embolization of cerebral aneurysms is a safe alternative to surgical clipping in the treatment of both ruptured and unruptured cerebral aneurysms; however, long-term outcome needs to be evaluated.

2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats.

2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and antiproapoptotic activities. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries might activate a unique signaling pathway, hypoxia-inducible factor-1alpha (HIF-1alpha), to produce or enhance cerebral vasospasm after subarachnoid hemorrhage (SAH). Sprague-Dawley male rats (n = 70) were randomly divided into 5 groups: Sham operated, SAH without treatment, SAH treated with vehicle (DMSO), SAH treated with two HIF-1alpha inhibitors, 2ME2, and D609 (positive control of 2ME2). SAH model was produced by middle cerebral artery perforation. 2ME2 and D609 were administered intraperitoneal at 1 h after SAH; rats were sacrificed after 48 h of SAH. Thick blood clot was observed around basilar artery under arachnoids in all animals except Sham group; severe morphological vasospasm was observed in basilar arteries in SAH and SAH+DMSO rats, and the mild vasospasm in rats treated with 2ME2 and D609; 2ME2 and D609 reduced the activity of HIF-1alpha in the basilar arteries by HIF-1alpha DuoSet ELISA; reduce the expression of HIF-1alpha, VEGF, BNIP3 and PCNA in basilar arteries by Western blotting and immunohistochemical staining. In addition, it decreased the mortality and improved the neurological deficits. In conclusion, 2ME2 is a powerful agent to reduce cerebral vasospasm by inhibiting HIF-1alpha activity and the expression of VEGF as its downstream, suppressing endothelium and VSMCs apoptosis via BNIP3 pathway, and attenuating vasoproliferation.

Trends in surgical and management outcomes in patients with aneurysmal subarachnoid hemorrhage in Izumo city, Japan, between 1980-1989 and 1990-1998.

BACKGROUND AND PURPOSE: The purpose of this community-based study was to evaluate temporal changes in surgical and management outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The subjects were 358 patients with aneurysmal SAH who were treated during the 19-year period from 1980 to 1998 in Izumo City, Japan. We compared data during the 9-year period 1990-1998 (period B; 188 patients) with those during the 10-year period 1980-1989 (period A; 170 patients). RESULTS: The proportion of patients 80 years of age or older or those with World Federation of Neurosurgical Societies grade V increased significantly (period A, 5 and 25%; period B, 18 and 35%, respectively). The operability rate did not change for patients 69 years of age or younger, whereas it increased significantly for those 70-79 years of age (period A, 48%; period B, 72%). The 6-month and 2-year case fatality rates in surgically treated patients decreased significantly (period A, 12 and 20%; period B, 2 and 8%, respectively), whereas they were virtually unchanged for overall management (period A, 41 and 46%; period B, 38 and 42%, respectively). In patients who underwent surgery, the incidence of permanent symptomatic vasospasm decreased from 21% during period A to 11% during period B, and there was no death from vasospasm in the later period. However, no significant difference was found in the functional outcome between the two periods, regardless of whether surgery was performed. The most important determinants of 6-month and 2-year survival rates were grade on admission, rebleeding and the site of the ruptured aneurysms. Age was also a significant predictor of the 6-month case fatality rate. CONCLUSIONS: For patients with SAH who underwent surgery, there were trends towards decreases in the case fatality rate and in the incidence of permanent symptomatic vasospasm. Nevertheless, the overall management outcome was still unsatisfactory, mainly because of increasing numbers of very elderly and/or high-risk patients. .