Prevention of vasospasm after subarachnoid hemorrhage in dogs by continuous intravenous infusion of PD156707.
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This randomized, blinded study tested the prophylactic effect of PD156707, a nonpeptide competitive antagonist of endothelin A receptors, against vasospasm after subarachnoid hemorrhage in dogs. Twenty-two dogs were allocated on day 0 to undergo cerebral angiography followed by injection of arterial blood (0.5 ml/kg) into the cisterna magna. Dogs had central venous catheters implanted for continuous infusion of drug vehicle (n = 10) or PD156707 (n = 12). Cisternal blood injection was repeated on day 2. Drug levels were measured in plasma on days 2, 4, 6, and 7 and in cerebrospinal fluid (CSF) on days 2 and 7. Angiography was repeated on day 7 to assess vasospasm. After angiography on day 7, acute effects of infusion of PD156707, 100 mg, or drug vehicle on established vasospasm were assessed. Analysis of physiological variables within (analysis of variance) groups across time and between (unpaired t-test) groups at each time showed that drug-treated animals had significantly increased heart rate on day 7 compared to day 0 (p < 0.005). Comparison of basilar artery diameters at day 7 showed that PD156707 significantly decreased the degree of basilar artery vasospasm (placebo: -47 +/- 5% reduction [mean +/- SE] versus PD156707: -28 +/- 7%, p < 0.05, unpaired t-test). There was, however, significant vasospasm when comparing within groups (paired t-test, placebo: p < 0.0001, PD156707: p < 0.005). Mean plasma PD156707 levels (322 +/- 123 ng/ml) were adequate to block responses of endothelin-1 on endothelin A receptors in vitro although CSF levels (11 +/- 7 ng/ml) were substantially lower. Infusion of PD156707 into the basilar artery on day 7 caused a small but significant 10 +/- 3% (paired t-test, p < 0.01) increase in diameter compared to placebo (3 +/- 3% increase, p = 0.32). This infusion also was associated with a substantial increase in CSF drug levels to 19 +/- 9 mg/ml. These results suggest that endothelin A receptors mediate some of the vasospasm that occurs after SAH in dogs and that blockade of these receptors may be a beneficial treatment for vasospasm. (+info)
The effect and management of delayed vasospasm after aneurysmal subarachnoid hemorrhage.
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Delayed cerebral vasospasm after aneurysm rupture is one of the major complications of subarachnoid hemorrhage. The purpose of this review was to determine the true incidence of vasospasm. All literature on cerebral aneurysms from 1960 onwards was reviewed, and the figures extracted from publications that mentioned vasospasm. Angiographic vasospasm, where patients were studied at the time of peak incidence, was reported in about two thirds of cases. Symptomatic vasospasm or delayed ischemia affects about one third. Untreated, nearly a third of those with ischemic deficits die and a similar proportion are left permanently disabled. Variations of Triple-H (hypervolemia, hypertension, hemodilution) therapy, used early after hemorrhage for prophylaxis of vasospasm, are associated with a decrease of nearly half in the incidence of delayed ischemia. When used as therapy outcome also appears better, with a reduction particularly in the death rate. Calcium antagonists have been widely used, especially nimodipine. In several controlled trials the incidence of delayed ischemia was significantly reduced. More importantly, the overall outcome of all subarachnoid hemorrhage patients was better with nimodipine prophylaxis. The 21-aminosteroid tirilazad mesylate has been the subject of several trials. In one the overall outcome of all patients was improved, but the effect was essentially in males only. Further studies with larger doses in females are being analyzed. (+info)
Angioarchitecture related to hemorrhage in cerebral arteriovenous malformations.
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A retrospective study was conducted to determine the angioarchitecture related to hemorrhage in patients with cerebral arteriovenous malformations (AVMs), who underwent conservative treatment and long-term follow-up. The average observation period was 9.3 years, and the annual bleeding rate was estimated at 3.6%. In all cases angiographic findings were reviewed in detail. The average AVM grade by Spetzler-Martin was 3.5. Higher bleeding rate was observed in large AVM (5.4%) compared with small (2.1%) or medium AVM (2.9%). Deep venous drainage (8.6%/year) was strongly correlated to hemorrhage. Concerning location of nidus, hemorrhage was frequently found in insular, callosal, and cerebellar AVMs. Venous ectasia, feeder aneurysm, and external carotid supply were commonly demonstrated on angiograms. Comparison of annual bleeding rate revealed that AVMs with intranidal aneurysm (8.5%) and venous stenosis (5.5%) had a high propensity to hemorrhage. Therapeutic strategy should be focused on these potentially hazardous lesions by the use of endovascular embolization or stereotactic radiosurgery, even if surgical resection is not indicated. (+info)
Fluid-attenuated inversion-recovery MR imaging in acute and subacute cerebral intraventricular hemorrhage.
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BACKGROUND AND PURPOSE: Fluid-attenuated inversion-recovery (FLAIR) MR imaging may show subarachnoid hemorrhage (SAH) with high sensitivity. We hypothesized that the FLAIR technique is effective and reliable in the diagnosis of cerebral intraventricular hemorrhage (IVH). METHODS: Two observers evaluated the 1.5-T MR fast spin-echo FLAIR images, T1- and T2-weighted MR images, and CT scans of 13 patients with IVH and the FLAIR images of 40 control subjects. RESULTS: IVH appeared bright on the FLAIR images obtained during the first 48 hours and was of variable appearance at later stages. FLAIR MR imaging detected 12 of 13 cases of IVH; no control subjects were falsely thought to have IVH (92% sensitivity, 100% specificity). However, IVH could not be fully excluded in the third ventricle (20%, n = 8) or in the fourth ventricle (28%, n = 11) on some control images because of CSF pulsation artifacts. Two cases had CT-negative IVH seen on FLAIR images. One case had FLAIR-negative IVH seen by CT. Although the sensitivities of conventional MR imaging (92%) and CT (85%) were also high, FLAIR imaging showed IVH more conspicuously than did standard MR imaging and CT in 62% of the cases (n = 8). FLAIR was as good as or better than CT in showing IVH in 10 cases (77%). FLAIR images showed all coexisting SAH. CONCLUSION: FLAIR MR imaging identifies acute and subacute IVH in the lateral ventricles with high sensitivity and specificity. In cases of subacute IVH, conventional MR imaging complements FLAIR in detecting IVH. The usefulness of the FLAIR technique for detecting third and fourth ventricular IVH may be compromised by artifacts. Blood hemoglobin degradation most likely causes the variable FLAIR appearance of IVH after the first 48 hours. (+info)
Subarachnoid haemorrhage: difficulties in diagnosis and treatment.
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Aneurysmal subarachnoid haemorrhage is associated with a uniquely severe headache of acute onset. Classical cases are readily identified as such, although this is not always the case. Four cases who were admitted to a district general hospital within a 3-month period are presented, because they demonstrate a variety of presentations, management options, and outcomes. (+info)
Risk of subarachnoid hemorrhage after surgical treatment of unruptured cerebral aneurysms.
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BACKGROUND AND PURPOSE: Recent progress in noninvasive imaging techniques has resulted in increased detection of unruptured aneurysms. Although many neurosurgeons advocate surgical intervention for such unruptured aneurysms, the long-term results of surgery for unruptured aneurysms have not been carefully investigated. METHODS: We analyzed 173 consecutive patients who had unruptured intracranial saccular aneurysm(s) detected by angiography that was performed for reasons other than subarachnoid hemorrhage (SAH). Of those, 115 cases were surgically treated and studied. All patients were followed up for either SAH, repeat treatment of aneurysms, or death. The median follow-up period was 8.8 years. RESULTS: Four of the 115 patients suffered SAH either from a de novo aneurysm (2) or from regrowth of clipped aneurysm (1), or from regrowth after wrapping (1). Additionally, 1 patient also suffered SAH from an unstudied basilar aneurysm. One patient was incidentally found to have de novo aneurysm and underwent reoperation 14 years after the first operation. The cumulative risk for SAH for the 114 cases excluding the basilar aneurysm case was 1.4% in 10 years and 12.4% in 20 years. CONCLUSIONS: Although this study confirmed the long-term efficacy of clipping unruptured aneurysms, the risk of SAH was high compared with that in the general population, even after treatment. Considering the high mortality rate of SAH, long-term follow-up by angiography may be warranted for patients with surgically treated unruptured aneurysms. (+info)
Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage.
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BACKGROUND AND PURPOSE: The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well. METHODS: Symptomatic vasospasm was defined as the association of deterioration in a patient's neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay. RESULTS: Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (P=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1. 77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae. CONCLUSIONS: Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments. (+info)
Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humans.
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BACKGROUND AND PURPOSE: The delayed type of cerebral vasoconstriction known as cerebral vasospasm (DCV) remains an important cause of permanent neurological injury and death following aneurysmal subarachnoid hemorrhage despite best current medical therapy. The mechanism of DCV remains unknown. A new treatment for refractory DCV using intrathecally delivered sodium nitroprusside and results in 21 patients is reported. METHODS: Candidates for treatment were patients with secured cerebral aneurysms presenting with clinical or radiographic SAH of grade 3 or higher. Patients with and without established DCV were treated. In 57% (12/21 patients) the diagnosis of severe DCV refractory to conventional treatment (HHH therapy and nimodipine) was established before treatment. Ten patients received ITSNP prophylactically. All patients with established DCV were in grave neurological condition before treatment. Procedures for vasospasm reversal were performed under simultaneous angiographic control with extensive hemodynamic and neurophysiologic monitoring. ITSNP was delivered by intraventricular or subdural catheter or by direct intraoperative suffusion. End points of intervention for established DCV were (1) durable angiographic reversal of vasoconstriction, (2) failure to effect reversal within 30 minutes, and (3) adverse effect. End points for DCV prevention were (1) post-SAH day 10 without evidence of vasoconstriction and (2) adverse effect. Cerebral angioplasty was used concomitantly in 9 treatments. The total number of treatments recorded was 171. RESULTS: The overall neurological outcome was good or excellent in 76% of patients (16/21) overall and in 88.9% of patients (16/18) having at least a 1-month follow-up. Of the 5 patients with less-than-good outcome, 4 had presented initially with severe neurological injury (clinical SAH grade 4). Angiography demonstrated reversal or amelioration of vasoconstriction in 83% (5/6 cases) of established DCV treated by ITSNP alone. Among patients treated prophylactically, none developed clinical DCV. CONCLUSIONS: These results suggest that ITSNP is a safe and potentially effective treatment for established DCV and cerebral ischemia refractory to conventional treatment. The preliminary results of prophylactic treatment are also favorable with regard to safety. (+info)