Method of aneurysm treatment does not affect clot clearance after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Patients undergoing neurosurgical clipping or endovascular coiling of a ruptured aneurysm may differ in their risk of vasospasm. OBJECTIVE: Because clot clearance affects vasospasm, we tested the hypothesis that clot clearance differs in patients depending on method of aneurysm treatment. METHODS: Exploratory analysis was performed on 413 patients from CONSCIOUS-1, a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). Clot clearance was measured by change in Hijdra score between baseline computed tomography and one performed 24 to 48 hours after aneurysm treatment. Angiographic vasospasm was assessed by the use of catheter angiography 7 to 11 days after SAH, and delayed ischemic neurological deficit (DIND) was determined clinically. Extended Glasgow Outcome Score (GOSE) was assessed 3 months after SAH, and poor outcome was defined as death, vegetative state, or severe disability. Multivariable ordinal and binary logistic regression were used. RESULTS: There was no significant difference in the rate of clot clearance between patients undergoing clipping or coiling (P = .56). Coiling was independently associated with decreased severity of angiographic vasospasm (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.33-0.86), but not with DIND or GOSE. Greater clot clearance decreased the risk of severe angiographic vasospasm (OR 0.86, 95% CI 0.81-0.91), whereas higher baseline Hijdra score predicted increased angiographic vasospasm (OR 1.17, 95% CI 1.11-1.23) and poor GOSE (OR 1.09, 95% CI 1.04-1.14). CONCLUSION: Aneurysm coiling and increased clot clearance were independently associated with decreased severity of angiographic vasospasm in multivariate analysis, although no differences in clot clearance were seen between coiled and clipped patients.

Attributing hypodensities on CT to angiographic vasospasm is not sensitive and unreliable.

BACKGROUND AND PURPOSE: The presence of low-density areas on CT is used in clinical decision-making regarding treatment of angiographic vasospasm as well as in research as a surrogate marker for severity of angiographic vasospasm. We assess the interobserver variability in attributing hypodensities on CT to angiographic vasospasm-related delayed ischemic neurological deficit. METHODS: Three experienced reviewers, 2 neurosurgeons, and a neuroradiologist independently reviewed CT scans of 413 patients enrolled in the Clazosentan to Overcome Neurological iSChemia and Infarction OccUrring after Subarachnoid hemorrhage (CONSCIOUS-1) trial, who universally underwent catheter angiography to determine severity of angiographic vasospasm. Interobserver variability was calculated using the κ statistic and the χ(2) test was used to determine associations between dichotomized outcomes. RESULTS: There was considerable interobserver variability in attributing CT hypodensities to vasospasm-related delayed ischemic neurological deficit (κ=0.51-0.78; 95% CI, 0.35-0.90). Patients with hypodensities attributed to delayed ischemic neurological deficit were significantly more likely to have severe angiographic vasospasm (P=0.001), but a substantial proportion of these patients (19%) also had mild or no spasm. CT hypodensities had a sensitivity and specificity of 41% and 93%, respectively, in identifying patients with severe angiographic vasospasm, even with expert consensus that these represent angiographic vasospasm-related delayed ischemic neurological deficit. CONCLUSIONS: We find considerable interobserver variability in attributing CT hypodensities to angiographic vasospasm and propose that they may not be a robust marker of severity of angiographic vasospasm, even with unanimous expert agreement that they are a result of vasospasm-related delayed ischemic neurological deficit. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00111085.

Feasibility of intraventricular nicardipine prolonged release implants in patients following aneurysmal subarachnoid haemorrhage.

OBJECTIVE: Intracisternal nicardipine prolonged release implants (NPRI) have been shown to be effective in the prophylaxis of cerebral vasospasm (VS). However, they cannot be used in patients following coil occlusion of the aneurysm. As a certain dissemination of nicardipine within the cerebrospinal fluid (CSF) has been described, we examined the feasibility of intraventricular use of NPRI in patients that underwent clip and coil occlusion of their aneurysms following aneurysmal subarachnoid haemorrhage (aSAH). By comparison with an historical control group, an estimation of their effectivity in regard to angiographic vasospasm and the development of cerebral infarction has been performed. METHODS: Thirty-one patients suffering from aSAH were prospectively included in this trial. Study participants received prior to clipping (n = 17) or coiling (n = 14) 6 (n = 15) or 10 NPRI (n = 16) into the lateral ventricles. Physiological data were collected, proximal and global VS were determined using pre-operative and day 8 ± 1 angiography, and incidence of hydrocephalus and VS related infarcts were evaluated and compared to a historical control group consisting of 16 operated patients without NPRI implantation. RESULTS: Intraventricular NPRI were tolerated well. There were no adverse side effects detectable, physiological variables such as heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP) and electrolytes showed no difference compared to control. There was no difference in the proportion of patients that required CSF shunting. A significant positive angiographic effect could only be observed in clipped patients (proximal vessel diameters: control, 80 ± 30%; NPRI 90 ± 24%; incidence of moderate/severe global VS: control, 73%; NPRI, 41%). CONCLUSIONS: The use of intraventricular NPRI seems to be safe and tolerated well. There is preliminary evidence for effectivity on angiographic VS for clipped patients only. A further increase of the effective dose might also exert efficacy in the subset of patients following coil occlusion.

Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The long-standing concept that delayed cerebral infarction after aneurysmal subarachnoid hemorrhage results exclusively from large artery vasospasm recently has been challenged. We used data from the CONSCIOUS-1 trial to determine the relationship between angiographic vasospasm and cerebral infarction after subarachnoid hemorrhage. METHODS: We performed a post hoc exploratory analysis of the CONSCIOUS-1 data. All patients underwent catheter angiography before treatment and 9±2 days after subarachnoid hemorrhage. CT was performed before and after aneurysm treatment, and 6 weeks after subarachnoid hemorrhage. Angiograms and CT scans were assessed by centralized blinded review. Angiographic vasospasm was classified as none/mild (0%-33% decrease in arterial diameter), moderate (34%-66%), or severe (≥67%). Infarctions were categorized as secondary to angiographic vasospasm, other, or unknown causes. Logistic regression was conducted to determine factors associated with infarction. RESULTS: Complete data were available for 381 of 413 patients (92%). Angiographic vasospasm was none/mild in 209 (55%) patients, moderate in 118 (31%), and severe in 54 (14%). Infarcts developed in 6 (3%) of 209 with no/mild, 12 (10%) of 118 patients with moderate, and 25 (46%) of 54 patients with severe vasospasm. Multivariate analysis found a strong association between angiographic vasospasm and cerebral infarction (OR, 9.3; 95% CI, 3.7-23.4). The significant association persisted after adjusting for admission neurological grade and aneurysm size. Method of aneurysm treatment was not associated with a significant difference in frequency of infarction. CONCLUSIONS: A strong association exists between angiographic vasospasm and cerebral infarction. Efforts directed at further reducing angiographic vasospasm are warranted.

Endovascular treatment or neurosurgical clipping of ruptured intracranial aneurysms: effect on angiographic vasospasm, delayed ischemic neurological deficit, cerebral infarction, and clinical outcome.

BACKGROUND AND PURPOSE: The effects of aneurysm treatment modality (clipping or coiling) on the incidence of cerebral vasospasm and infarction after subarachnoid hemorrhage have not been clearly defined. We hypothesized that there may be a difference in angiographic and clinical vasospasm, cerebral infarction, and clinical outcome between patients undergoing clipping compared to coiling. METHODS: A retrospective, exploratory analysis of 413 patients randomized into the CONSCIOUS-1 trial was conducted. Patients underwent baseline and follow-up catheter angiography and computed tomography, as well as clinical assessments. Radiology end points were adjudicated by central blinded review, and angiographic vasospasm was quantified by measurements of arterial diameters on catheter angiography. The effect of method of aneurysm treatment (clipping [n=199] or coiling [n=214]) on angiographic vasospasm, delayed ischemic neurological deficit, cerebral infarction, and clinical outcome was analyzed using univariate and multivariate logistic regression. Propensity matching was used to adjust for differences in baseline risk factors between clipped and coiled patients. RESULTS: In all patients and the propensity-matched subset, aneurysm coiling was associated with a significantly reduced risk of angiographic vasospasm and delayed ischemic neurological deficit compared to clipping. Cerebral infarction and clinical outcome were not associated with clipping or coiling. CONCLUSIONS: In this exploratory analysis, aneurysm coiling was associated with less angiographic vasospasm and delayed ischemic neurological deficit than surgical clipping, whereas no effect on cerebral infarction or clinical outcome was observed. Whether this is attributable to differences in baseline risk factors between clipped and coiled patients or a true difference cannot be proven here.

Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 database.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) may develop after aneurysmal subarachnoid hemorrhage (SAH). We investigated factors associated with SIRS after SAH, whether SIRS was associated with complications of SAH such as vasospasm, cerebral infarction, and clinical outcome, and whether SIRS could contribute to a difference in outcome between patients treated by endovascular coiling or neurosurgical clipping of the ruptured aneurysm. METHODS: This was exploratory analysis of 413 patients in the CONSCIOUS-1 study. SIRS was diagnosed if the patient had at least 2 of 4 variables (hypothermia/fever, tachycardia, tachypnea, and leukocytosis/leukopenia) within 4 days of admission. Clinical outcome was measured on the Glasgow outcome scale 3 months after SAH. The relationship between clinical and radiologic variables and SIRS, angiographic vasospasm, delayed ischemic neurologic deficit (DIND), cerebral infarction, vasospasm-related infarction, and clinical outcome were modeled with uni- and multivariable analyses. RESULTS: 63% of patients developed SIRS. Many factors were associated with SIRS in univariate analysis, but only poor WFNS grade and pneumonia were independently associated with SIRS in multivariable analysis. SIRS burden (number of SIRS variables per day over the first 4 days) was associated with poor outcome, but not with angiographic vasospasm, DIND, or cerebral infarction. The method of aneurysm treatment was not associated with SIRS. CONCLUSION: SIRS was associated with poor outcome but not angiographic vasospasm, DIND, or cerebral infarction after SAH in the CONSCIOUS-1 data. There was no support for the notion that neurosurgical clipping is associated with a greater risk of SIRS than endovascular coiling.

Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial.

BACKGROUND AND PURPOSE: This randomized, double-blind, placebo-controlled, dose-finding study assessed efficacy and safety of 1, 5, and 15 mg/h intravenous clazosentan, an endothelin receptor antagonist, in preventing vasospasm after aneurysmal subarachnoid hemorrhage. METHODS: Patients (n=413) were randomized to placebo or clazosentan beginning within 56 hours and continued up to 14 days after initiation of treatment. The primary end point was moderate or severe angiographic vasospasm based on centrally read, blinded evaluation of digital subtraction angiography at baseline and 7 to 11 days postsubarachnoid hemorrhage. A morbidity/mortality end point, including all-cause mortality, new cerebral infarct from any cause, delayed ischemic neurological deficit due to vasospasm, or use of rescue therapy, was evaluated by local assessment. Clinical outcome was assessed by the extended Glasgow Outcome Scale at 12 weeks. RESULTS: Moderate or severe vasospasm was reduced in a dose-dependent fashion from 66% in the placebo group to 23% in the 15 mg/h clazosentan group (risk reduction, 65%; 95% CI, 47% to 78%; P<0.0001). No significant effects were seen on secondary end points. Post hoc analysis using a centrally assessed morbidity/mortality end point that included death and rescue therapy but only cerebral infarcts and delayed ischemic neurological deficit due to vasospasm on central review showed a trend toward improvement with clazosentan (37%, 28%, and 29% in the 1, 5, and 15 mg/h groups versus 39% in the placebo group, nonsignificant). Clazosentan was associated with increased rates of pulmonary complications, hypotension, and anemia. CONCLUSIONS: Clazosentan significantly decreased moderate and severe vasospasm in a dose-dependent manner and showed a trend for reduction in vasospasm-related morbidity/mortality in patients with aneurysmal subarachnoid hemorrhage when centrally assessed. Overall, the adverse effects were manageable and not considered serious.

Effect of nicardipine prolonged-release implants on cerebral vasospasm and clinical outcome after severe aneurysmal subarachnoid hemorrhage: a prospective, randomized, double-blind phase IIa study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effect of nicardipine prolonged-release implants (NPRIs) on cerebral vasospasm and clinical outcome after severe subarachnoid hemorrhage. METHODS: Thirty-two patients with severe subarachnoid hemorrhage and undergoing aneurysm clipping were included into this single center, randomized, double-blind trial. Sixteen patients received NPRIs implanted into the basal cisterns in direct contact to the exposed proximal blood vessels; in 16 control patients, the basal cisterns were opened and washed out only without leaving implants. Angiography was performed preoperatively and at day 8+/-1. Computed tomography imaging was analyzed for the incidence of territorial infarcts unrelated to surgery. Patient outcome was assessed using the modified Rankin and National Institute of Health Stroke scales. RESULTS: The incidence of angiographic vasospasm in proximal vessel segments was significantly reduced after implantation of NPRIs (73% control versus 7% NPRIs). Significant differences occurred also for the majority of distal vessel segments. Computed tomography scans revealed a lower incidence of delayed ischemic lesions (47% control versus 14% NPRIs). The NPRI group demonstrated more favorable modified Rankin and National Institute of Health Stroke scales as well as a significantly lower incidence of deaths (38% control versus 6% NPRIs). CONCLUSIONS: Implantation of NPRIs reduces the incidence of cerebral vasospasm and delayed ischemic deficits and improves clinical outcome after severe subarachnoid hemorrhage.

Cyst of the third ventricle as an unusual cause of acquired hydrocephalus.

Cysts of the third ventricle are rare congenital suprasellar malformations of arachnoidal, endodermal, or neuroepithelial origin. Depending on their size and location, they can cause space-occupying intracranial lesions and hydrocephalus occlusus by obstruction of the aqueduct or foramen of Monro. They can be missed on routine computer tomography and magnetic resonance imaging. A 2-year-old boy presented signs of intracranial pressure. Initial magnetic resonance imaging revealed a triventricular internal hydrocephalus with no visible etiologic lesion. An extended investigation with the constructive interference in steady state-technique showed a mobile cystic cerebrospinal fluid-intense lesion within the third ventricle, causing transient occlusion of the foramen of Monro. A suprasellar cyst of the third ventricle is an important differential diagnosis in apparently "idiopathic" internal hydrocephalus. In such cases, magnetic resonance imaging using the constructive interference in steady state-technique with a slice thickness of 1 mm is the method of choice for detecting intraventricular cysts. Neurosurgical fenestration and/or resection of the cyst by neuroendoscopy can resolve cerebrospinal fluid circulation disturbances and seems to be superior to a shunt.