Does treatment modality of intracranial ruptured aneurysms influence the incidence of cerebral vasospasm and clinical outcome?

BACKGROUND: Cerebral vasospasm is the most common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). This study is designed to determine whether the incidence of symptomatic vasospasm and the overall clinical outcome differ between patients treated with surgical clipping compared with endovascular obliteration of aneurysms. METHODS: In this prospective study, 98 patients with aneurysmal SAH were treated. Seventy-two patients underwent surgery and clipping and 26 had coil embolization. The incidence of symptomatic vasospasm, permanent neurologic deficit due to vasospasm and clinical outcome were analyzed. Patients with better clinical and radiological grades (World Federation of Neurological Surgeons grades I-III and Fisher grades I-III) were analyzed separately. RESULTS: Symptomatic vasospasm occurred in 22% of the patients; 25% in the surgical group and 15% in the endovascular group. Nine percent of the patients in the surgical group and 7% in the endovascular group suffered ischemic infarction with permanent neurological deficit. These differences did not reach statistical significance (p = 0.42). For patients with better clinical and radiological grades, no significant difference was found for the rate of symptomatic vasospasm; 23% in the surgical and 12% in the endovascular group (p = 0.49). The overall clinical outcome was comparable in both groups, with no difference in the likelihood of a Glasgow Outcome Scale score of 3 or less (15% in the surgical and 16% in the endovascular group; p = 0.87). The same results for outcome were obtained for the subgroup of patients with better clinical grades on admission. CONCLUSION: Symptomatic vasospasm and ischemic infarction rate seem comparable in both groups, even for patients with better clinical and radiological admission grades. There is no significant difference in the overall clinical outcome at the long-term follow-up between both groups.     

A double-blind clinical evaluation of the effect of Nizofenone (Y-9179) on delayed ischemic neurological deficits following aneurysmal rupture

The effect of Nizofenone (Y-9179), a vertebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trials. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors. In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm. Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p less than 0.05). No particular side effect of Nizofenone was observed. Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.     

Hunt-Hess Ⅰ～Ⅲ级动脉瘤性蛛网膜下腔出血早期手术术前腰大池外引流的临床观察

目的 探讨Hunt-Hess Ⅰ～Ⅲ级动脉瘤性蛛网膜下腔出血(SAH)早期手术术前腰大池外引流的临床疗效.方法 将早期手术的Hunt-Hess Ⅰ～Ⅲ级动脉瘤性SAH患者分为术前腰大池外引流组(47例)和术后腰大池外引流组(54例),分析两组病例的疗效差异.结果 术前腰大池外引流组无置管导致的动脉瘤再破裂出血病例,其术中动脉瘤破裂、症状性脑血管痉挛、慢性脑积水的发生率分别为8.5%、12.8%、12.8%,均低于术后腰大池外引流组的11.1%、20.4%、14.8%.结论 术前行腰大池外引流无增加Hunt-Hess Ⅰ～Ⅲ级动脉瘤性SAH早期手术患者动脉瘤再破裂出血的风险,并且可降低症状性脑血管痉挛和慢性脑积水的发生率.

Abstract：

Objective To explore the therapeutic effect of preoperative external hunbar drainage in Hunt and Hess grade Ⅰ～Ⅲ patients with subarachnoid hemorrhage ( SAH ) undergoing early surgery for intracranial aneurysms. Method The 101 cases of grade Ⅰ～Ⅲ patients according to the classification of Hunt and Hess with early surgical treatment were devided into preoperative external lumbar drainage group(47 cases) and postoperative external lumbar drainage group(54 cases).Outcome of patients with different external drainage of cerebrospinal fluid was analyzed. Results There was no case of aneurysm rebleeding could be associated with preoperative spinal drain placement. Tne incidences of intraoperative aneurysm rapture in preoperative external lumbar drainage group was 8. 5%,which was lower than 11. 1% in postoperative external lumbar drainage group. The incidences of symptomatic cerebral vasospasm and chronic hydrocephalus in preoperative external lumbar drainage group were 12. 8% and 12.8% ,which were lower than 20. 4% and 14. 8% in postoperative external lumbar drainage group. There all were not significant differences between the two groups. Conclusions Preoperative external lumbar drainage wont increase a risk of rebleeding for grade Ⅰ～Ⅲ patients with aneurysmal SAH undergoing early surg ery. Furthermore, it can decrease the incidences of symptomatic cerebral vasospasm and chronic hydrocephalus,which is a safe and useful method of removing bloody cerebrospinal fluid.     

Prevention of symptomatic vasospasm after SAH by constant venous infusion of nimodipine

Sixty-one patients with SAH due to rupture of a cerebral aneurysm, classified in Grades I to IV according to Hunt and Hess, received a constant venous infusion of Nimodipine in a dose of 2mg/h for at least 14 days, followed by an oral administration of 60 mg/6 h for at least 4 days. Patients admitted after the 6th day of SAH, patients with SAH but without aneurysm on the angiogram and patients in Grade V were excluded. Mortality in 30 patients of Grades I-II was 3.3%, in 31 patients of Grades III-IV 42%. In the latter group 1 patient died due to cerebral vasospasm. Transient vasospasm occurred in 2 patients of Grades I-II. Recovery was complete in both cases. Thus, incidence of cerebral vasospasm was 4.9%, the incidence of poor-outcome-vasospasm even only 1.6%. The syndrome of cerebral vasospasm seems to be more than only constriction of cerebral vessels. The deleterious effects of Ca2+ shift into vascular cells and into neural cells which causes irreversible damage are discussed. Early administration of a specific 'cerebral' calcium antagonist like Nimodipine after SAH will prevent the intracellular Ca2+ overloading, thus protecting the neural cells and preventing Ca2+-induced smooth-muscle contraction of cerebral vessels, which encourages ischaemic deficits after SAH. The preventive use of Nimodipine has markedly reduced the incidence of symptomatic vasospasm in our clinic.     

Acute Ischemic Injury on Diffusion-Weighted Magnetic Resonance Imaging after Poor Grade Subarachnoid Hemorrhage

Background

Poor clinical condition is the most important predictor of neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture of an intracranial aneurysm was shown to be associated with acute ischemic brain injury in poor grade patients in autopsy studies and small magnetic resonance imaging series.

Methods

We performed diffusion-weighted magnetic resonance imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt–Hess grade 4 or 5 enrolled in the Columbia University SAH Outcomes Project between July 2004 and February 2007. We analyzed demographic, radiological, clinical data, and 3 months outcome.

Results

Of the 21 patients 13 were Hunt–Hess grade 5, and eight were grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities on DWI, but not on computed tomography (CT). Involved regions included both anterior cerebral artery territories (16 patients), and less often the thalamus and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were dead (life support had been withdrawn in 6), 2 were moderately to severely disabled (modified Rankin Scale [mRS] = 4–5), and 4 had moderate-to-no disability (mRS = 1–3).

Conclusions

Admission DWI demonstrates multifocal areas of acute ischemic injury in poor grade SAH patients. These ischemic lesions may be related to transient intracranial circulatory arrest, acute vasoconstriction, microcirculatory disturbances, or decreased cerebral perfusion from neurogenic cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible target for acute resuscitation strategies.     

A Double-blind Clinical Evaluation of the Effect of Nizofenone (Y-9179) on Delayed Ischemic Neurological Deficits Following Aneurysmal Rupture

The effect of Nizofenone (Y-9179), a verebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trial. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors.

In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm.

Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p < 0.05). No particular side effect of Nizofenone was observed.

Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.     

载瘤动脉临时阻断处理颅内动脉瘤的临床研究

目的 探讨载瘤动脉临时阻断处理动脉瘤继发缺血性脑功能损伤的相关因素。方法 63例颅内动脉瘤夹闭过程中行载瘤动脉临时阻断，术后根据相应部位有无脑功能障碍，CT检查阻断血管供应区有无新鲜梗塞灶为标准判断是否造成缺血性脑损伤，并按有无蛛网膜下腔出血、动脉瘤所在部位、Hunt和Hess分级等进行分组对照。结果 63例载瘤动脉临时阻断时间3-59min，术后共有12例出现缺血性脑损伤表现，其中术前有蛛网膜下腔出血(SAH)者11例，Hunt和Hess分级Ⅲ～V者8例，基底动脉5例、大脑中动脉4例。阻断时间16min以内者均无缺血性脑损伤。结论 载瘤动脉临时阻断继发缺血性脑损伤与阻断部位、阻断时间、阻断方式、侧支循环的个体差异、病人术前状况等因素有关。     

Noninvasive measurement of cerebral vasopasm in patients with subarachnoid hemorrhage

Regional cerebral blood flow (rCBF) was measured as fast flow clearance (F1) and the initial slope index (ISI2) after inhalation of 133Xe in 30 patients with subarachnoid hemorrhage (SAH). Vasomotor responsiveness to reduction in end-tibal PECO2 was examined in those patients who could carry out this procedure satisfactorily as a test for the presence or absence of vasospasm. F1 and ISI2 were significantly reduced in patients with recent SAH compared to 35 age-matched normal volunteers. The degree of reduction of F1 and ISI2 correlated directly with severity of the neurological deficit graded according to the Hunt and Hess rating scale. Topographic reductions of rCBF correlated with angiographically demonstrated vasospasm or intracerebral hematoma. The degree of impairment of cerebral vasomotor responsiveness to reduction of PECO2 by hyperventilation also correlated with the severity of vasospasm demonstrated angiographically in 16 patients. The reductions of rCBF values were maximal during the first week after SAH but returned gradually toward normal by the 5th week. Individual patients with SAH whose lowest F1 values were above 50 ml/100 g brain/min tolerated surgical intervention best. Non-invasive measurements of rCBF after SAH appear to be helpful in estimating the presence and time course of vasospasm, in recognizing the development of normal pressure hydrocephalus, and in planning medical and surgical management.     

A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part I: Incidence and effects

Delayed ischaemia due to cerebral 'vasospasm' is a significant cause of morbidity and mortality after aneurysm haemorrhage. In a literature review more than 30 000 cases were found where vasospasm after subarachnoid haemorrhage (SAH) was discussed. The incidence of angiographic vasospasm was 43.3% overall, and 67.3% where angiography was done at a time of maximum expected spasm. Symptomatic vasospasm or delayed ischaemic deficit (DID) occurred in 32.5%. There was no difference in incidence and time course between preoperative and postoperative cases. 30% of those with DID died, and permanent neurological deficits occurred in 34%. A fatal outcome was much more likely in the presence of vasospasm, and a satisfactory outcome one third less likely. Vasospasm is thus the cause of death in about 10%, and of disability in slightly more cases of aneurysmal SAH. The extent of the problem has not changed significantly over three decades.     

Prevention of symptomatic vasospasm after SAH by constant venous infusion of nimodipine

Sixty-one patients with SAH due to rupture of a cerebral aneurysm, classified in Grades I to IV according to Hunt and Hess, received a constant venous infusion of Nimodipine in a dose of 2mg/h for at least 14 days, followed by an oral administration of 60 mg/6 h for at least 4 days. Patients admitted after the 6th day of SAH, patients with SAH but without aneurysm on the angiogram and patients in Grade V were excluded. Mortality in 30 patients of Grades I-II was 3.3%, in 31 patients of Grades III-IV 42%. In the latter group 1 patient died due to cerebral vasospasm. Transient vasospasm occurred in 2 patients of Grades I-II. Recovery was complete in both cases. Thus, incidence of cerebral vasospasm was 4.9%, the incidence of poor-outcome-vasospasm even only 1.6%. The syndrome of cerebral vasospasm seems to be more than only constriction of cerebral vessels. The deleterious effects of Ca²⁺ shift into vascular cells and into neural cells which causes irreversible damage are discussed. Early administration of a specific 'cerebral' calcium antagonist like Nimodipine after SAH will prevent the intracellular Ca²⁺ overloading, thus protecting the neural cells and preventing Ca²⁺-induced smooth-muscle contraction of cerebral vessels, which encourages ischaemic deficits after SAH. The preventive use of Nimodipine has markedly reduced the incidence of symptomatic vasospasm in our clinic.     

Doppler ultrasound measurement of blood flow volume in the extracranial internal carotid artery for evaluation of brain perfusion after aneurysmal subarachnoid hemorrhage

Monitoring of cerebral blood flow (CBF) is an essential part in the early diagnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Several methods have been established to monitor cerebral perfusion in these patients. During last few years, a new sonographic approach has been introduced, the so called 'angle independent ultrasound system' for monitoring volume flow in the internal carotid artery (ICA). The angle independent Doppler ultrasound system Quantix ND (Cardiosonix Ltd, Israel) determines the diameter of the ICA as well as the velocity of blood flow in the extracranial part of this vessel. Thus, a determination of the global CBF in the anterior circulation can be achieved. Aim of our study was to compare the Quantix ND system and the commonly used transcranial Doppler sonography (TCD) in patients suffering from aneurysmal SAH. We included 11 patients (eight female and three male; Hunt and Hess I-V) and performed post-operatively/post-interventionally daily measurement of blood flow volume in the ICA, and determined the blood flow velocity in middle and anterior cerebral artery (MCA and ACA) with TCD. Six patients post-operatively/post-interventionally developed cerebral vasospasm, resulting in ischemia and territorial infarction. Three patients were chosen as case studies. In contrast to the TCD, we found a strong significant correlation of blood flow volume with Quantix ND in the ICA and the occurrence of cerebral infarction (p<0.001). These preliminary data justify further investigation of this angle independent Doppler ultrasound device. We postulate that this new tool might be effective for monitoring the CBF in the critical post-operative/post-interventional interval following aneurysmal SAH.     

Diffusion- and perfusion-weighted imaging in vasospasm after subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Better measures of cerebral tissue perfusion and earlier detection of ischemic injury are needed to guide therapy in subarachnoid hemorrhage (SAH) patients with vasospasm. We sought to identify tissue ischemia and early ischemic injury with combined diffusion-weighted (DW) and hemodynamically weighted (HW) MRI in patients with vasospasm after SAH. METHODS: Combined DW and HW imaging was used to study 6 patients with clinical and angiographic vasospasm, 1 patient without clinical signs of vasospasm but with severe angiographic vasospasm, and 1 patient without angiographic spasm. Analysis of the passage of an intravenous contrast bolus through brain was used to construct multislice maps of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and tissue mean transit time (tMTT). We hypothesize that large HW imaging (HWI) abnormalities would be present in treated patients at the time they develop neurological deficit due to vasospasm without matching DW imaging (DWI) abnormalities. RESULTS: Small, sometimes multiple, ischemic lesions on DWI were seen encircled by a large area of decreased rCBF and increased tMTT in all patients with symptomatic vasospasm. Decreases in rCBV were not prominent. MRI hemodynamic abnormalities occurred in regions supplied by vessels with angiographic vasospasm or in their watershed territories. All patients with neurological deficit showed an area of abnormal tMTT much larger than the area of DWI abnormality. MRI images were normal in the asymptomatic patient with angiographic vasospasm and the patient with normal angiogram and no clinical signs of vasospasm. CONCLUSIONS: We conclude that DW/HW MRI in symptomatic vasospasm can detect widespread changes in tissue hemodynamics that encircle early foci of ischemic injury. With additional study, the technique could become a useful tool in the clinical management of patients with SAH.     

Bedside-microdialysis for early detection of vasospasm after subarachnoid hemorrhage. Case report and review of the literature

Continuous monitoring of cerebral metabolism would be desirable for early detection of vasospasm in SAH patients. Bedside-microdialysis, a new technique for on-line monitoring of cerebral metabolism, may reflect changes seen in cerebral vasospasm diagnosed by transcranial Doppler sonography (TCD). This report represents the first case of combined TCD monitoring and on-line microdialysis from the brain extracellular fluid in a SAH patient. A 48-year-old woman suffered subarachnoid hemorrhage grade IV according to Hunt and Hess. Angiography revealed an aneurysm of the left carotid artery. The aneurysm was clipped 45 hours after bleeding. The microdialysis catheter was inserted after aneurysm clipping into the white matter of the left temporal lobe. Sampling of microdialysates started immediately, analyzing time for glucose, lactate, pyruvate and glutamate was four minutes. Postoperatively, the patient was doing well and microdialysis and TCD parameters remained within normal range. On the third postoperative day a shift to anaerob metabolism (decrease of glucose, increase of lactate and the lactate-pyruvate ratio up to pathological levels) and an increase in glutamate was observed suggesting insufficient cerebral perfusion. The patient progressively deteriorated clinically. Vasospasm was diagnosed by TCD monitoring 36 hours after onset of ischemic changes monitored by microdialysis. After elevation of mean arterial blood pressure, TCD values and metabolic parameters normalized. Interestingly, the pathological changes in on-line microdialysis preceded the typical increase in blood flow velocity by TCD and the clinical deterioration. Our case suggests, that bedside-microdialysis may be useful for early detection of vasospasm and continuous surveillance of treatment and may be a new guide to treat ischemic neurological deficits following SAH.     

The relation between cerebral blood flow velocities as measured by TCD and the incidence of delayed ischemic deficits. A prospective study after subarachnoid hemorrhage

Patients (n = 127) with aneurysmal subarachnoid hemorrhage (SAH) were examined by transcranial Doppler ultrasonography (TCD) in a prospective study to follow the time course of the posthemorrhagic blood flow velocity in both the middle cerebral artery (MCA) and in the anterior cerebral artery (ACA). Results were analysed to reveal their relationship and predictive use with respect to the occurrence of delayed ischemic deficits. Mean flow velocities (MFV) higher than 120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA were interpreted as indicative for significant vasospasm. In 20 of our 127 patients (16%) a delayed ischemic deficit (DID) was subsequently diagnosed clinically (DID+ group). Patients in the DID+ group can be characterized as those individuals who presented early during the observation period post-SAH with highest values of MFV, a faster increase and longer persistence of pathologically elevated MFV-values (exceeding 120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA). They also show a greater difference in MFV-values if one compares the operated to the nonoperated side. Differences in MFV-values obtained in MCA or ACA were statistically significant (p < 0.05) for DID+ and DID- patients. The daily maximal increase of MFV was found between days 9 and 11 after SAH. In the DID+ group, the maximal MFV was 181 +/- 26 cm sec(-1) in MCA and 119 +/- 14 cm sec(-1) in ACA. In contrast to this, patients in the DID- group were found to present with MFV of 138 +/- 11 cm sec(-1) in MCA and 100 +/- 7 cm sec(-1) in ACA respectively. Delayed ischemic deficits appeared three times more often in DID+ patients than in patients with MFV < 120 cm sec(-1), if they showed a MFV > 120 cm sec(-1) in MCA. If pathological values were obtained in ACA, this ratio increases to about four times, if DID + patients presented with MFV > 90 cm sec(-1) versus patients with MFV < 90 cm sec(-1). Daily monitoring of vasospasm using TCD examination is thus helpful to identify patients at high risk for delayed ischemic deficits. This should allow us to implement further preventive treatment regimens.     

Serum magnesium levels as related to symptomatic vasospasm and outcome following aneurysmal subarachnoid hemorrhage

Introduction: Recent evidence suggests that magnesium may be neuroprotective in the setting of cerebral ischemia, and therapeutic magnesium infusion has been proposed for prophylaxis and treatment of delayed ischemic neurological deficit (DIND) resulting from vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). We studied the association between serum magnesium levels, the development of DIND, and the outcomes of patients with SAH. Methods: We studied 128 consecutive patients with aneurysmal SAH treated at our institution between 1990 and 1997 who had a serum magnesium level measured at least once during the acute phase of their hospitalization. Delayed ischemic neurological deficit was defined as severe (major focal deficit or coma), moderate (incomplete focal deficit or decreased sensorium without coma), or none.     

Does intraoperative aneurysm rupture influence outcome? Analysis of 169 patients

OBJECTIVES: The aim of this study was to evaluate the prognostic value of intraoperative aneurysm rupture (IAR) in patients with subarachnoid hemorrhage (SAH) undergoing surgery for cerebral aneurysms. PATIENTS AND METHODS: Between July 1997 and April 2000, 292 consecutive patients were admitted to our institution with SAH due to ruptured intracranial aneurysms. Of these, 169 patients were treated surgically according to standard microsurgical procedures and were included in this study. Mean age was 47 years. Initial clinical state was graded according to the classification of Hunt and Hess (HH). Outcome was classified according to the Glasgow Outcome Scale as favorable (grades IV and V) and unfavorable (grades I-III). Outcome of patients with intraoperative ruptured and non-ruptured aneurysms was analyzed in correlation to the preoperative clinical state and with respect to the time of surgery and to aneurysm localization. RESULTS: Different rupture rates were observed with respect to the localization of the aneurysm: anterior circulation (n=69) 39.1%, middle cerebral artery (n=46) 34.8%, internal carotid artery (n=48) 31.2%, and posterior circulation (n=6) 16.7%. Patients with HH-grades I-III showed a favorable outcome in 72.2% (61 of 84 patients) without intraoperative rupture and in 71.7% (33 of 46 patients) with intraoperative aneurysm rupture. The corresponding values for patients with HH-grades IV/V were: favorable outcome in 34.6% (9 of 26 patients) and 23.1% (3 of 13 patients), respectively. Poor initial clinical condition (HH IV and V) as well as the initial Fisher grades III and IV were strongly associated with poor clinical outcome. CONCLUSIONS: Intraoperative aneurysm rupture has no impact on the outcome, neither in patients with good initial condition nor for poor grades patients.     

Impact of Percutaneous Transluminal Angioplasty for Treatment of Cerebral Vasospasm on Subarachnoid Hemorrhage Patient Outcomes

Background

Percutaneous transluminal angioplasty (PTA) has been introduced for treatment of symptomatic cerebral vasospasm in patients with subarachnoid hemorrhage (SAH). While angiographic improvement is consistently reported, clinical improvement following the procedure varies, and limited data is available regarding overall impact on outcome.

Methods

The authors performed a retrospective analysis of all hospital admissions with aneurysmal SAH over a 6 year period. The length of stay, discharge outcomes (measured by modified Rankin scale [mRS] at discharge), and 1-year mortality among patients with SAH before (4 year period) and after (2 year period) institution of PTA for cerebral vasospasm were compared. Embolization for intracranial aneurysm was used as a therapeutic option throughout the study duration. The effect of institution of PTA for vasospasm after adjusting for age, clinical severity, and use of aneurysm embolization on both discharge outcomes and 1-year mortality in multivariate analysis was evaluated.

Results

A total of 146 patients with aneurysmal SAH were admitted during the study duration. There was no difference between the 89 patients admitted in pre-angioplasty period and 57 patients admitted in post-angioplasty period in regards to age, medical co-morbidities, and admission clinical severity of patients (measured by Hunt and Hess grade and Glasgow coma scale). A total of 18 (32%) patients underwent PTA with or without intra-arterial vasodilator treatment in the second period of the study. There was a non significant decrease in rates of severe disability and death (mRS 5–6) at discharge (45 vs. 33%, P = 0.09) and 1-year mortality (32 vs. 22%, P = 0.26) after introduction of PTA for cerebral vasospasm after adjusting for potential confounders. There was no significant difference between the two time periods in regards to length of stay.

Conclusion

A non significant trend was noted with reduced rate of severe disability and mortality at discharge and 1-year mortality after the introduction of PTA for cerebral vasospasm associated with SAH without increasing the length of hospital stay.     

Blood flow velocities in middle cerebral artery branches after subarachnoid hemorrhage.

In a prospective study, 55 patients were examined by transcranial duplex sonography (TCCS) after subarachnoid hemorrhage (SAH) to determine whether additional transcranial duplex examination on the middle cerebral artery M2 segments would aid in the examination of the MCA stem segment. The mean blood flow velocities and pulsatility index were correlated to the occurrence of delayed ischemic neurologic deficits (DIND). Out of 47 patients included, 21 did not experience any delayed deficit (group I), 15 did (group II), and in 11 the extent to which vasospasm contributed to a neurologic deficit was unclear (group III). The highest blood flow velocity and the greatest increase of mean blood flow velocity on 1 day were significantly higher in groups II and III both in M1 and in M2. In 10 patients in group II, where the onset day of DIND was known exactly, Doppler data indicating ischemia before or at the time of DIND were observed in nine. In eight patients, Doppler of the MCA stem alone would have provided enough information to recognize the risk of symptomatic vasospasm; in one patient, only the M2 Doppler gave an indication of ischemic complication. Transcranial duplex sonography may provide additional information to TCD by accurate delineation of M1/M2 vasospasm and therefore may help plan cerebral angiography and neurointerventional treatment.     

From bench-to-bedside in catastrophic cerebrovascular disease: development of drugs targeting the endothelin axis in subarachnoid hemorrhage-related vasospasm

Survivors of aneurysmal subarachnoid hemorrhage (SAH) may suffer functional dependence, cognitive impairment, and mood disorders. Cerebral vasospasm and delayed cerebral ischemia are associated with poor outcome in SAH and have been the subjects of intense investigation for decades. Recently a series of clinical trials was performed in SAH patients using an endothelin receptor antagonist. The results of these trials emphasize the disconnect between attenuation of cerebral vasospasm and improvement in functional outcome. The purpose of this review article is to evaluate the utilization of animal models for the development of drugs targeting the endothelin pathway in SAH and, given the recent endothelin receptor antagonist clinical trial results and lessons from the ischemic neuroprotection field, reflect on an alternative approach to in vivo preclinical drug testing in SAH.     

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.