Radiographic Vasospasm Research Articles

Preconditioning Effect on Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage

Recent experimental evidence indicates that endogenous mechanisms against cerebral vasospasm can be induced via preconditioning. To determine whether these vascular protective mechanisms are also present in vivo in humans with aneurysmal subarachnoid hemorrhage. A multicenter retrospective cohort of patients with aneurysmal subarachnoid hemorrhage was examined for ischemic preconditioning stimulus: preexisting steno-occlusive cerebrovascular disease (CVD) and/or previous cerebral infarct. Generalized estimating equation models were performed to determine the effect of the preconditioning stimulus on the primary end points of radiographic vasospasm, symptomatic vasospasm, and vasospasm-related delayed cerebral infarction and the secondary end point of discharge modified Rankin Scale score. Of 1043 patients, 321 (31%) had preexisting CVD and 437 (42%) had radiographic vasospasm. Patients with preexisting CVD were less likely to develop radiographic vasospasm (odds ratio = 0.67; 95% confidence interval = 0.489-0.930; P = .02) but had no differences in other end points. In terms of the secondary end point, patients with preexisting CVD did not differ significantly from patients without preexisting CVD in mortality or unfavorable outcome in multivariate analyses, although patients with preexisting CVD were marginally more likely to die (P = .06). This retrospective case-control study suggests that endogenous protective mechanisms against cerebral vasospasm-a preconditioning effect-may exist in humans, although these results could be the effect of atherosclerosis or some combination of preconditioning and atherosclerosis. Additional studies investigating the potential of preconditioning in aneurysmal subarachnoid hemorrhage are warranted.

The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot thickness, and incidence of radiographic or symptomatic vasospasm in patients enrolled in a prospective randomized controlled trial

Cerebral vasospasm following subarachnoid hemorrhage (SAH) causes significant morbidity in a delayed fashion. The authors recently published a new scale that grades the maximum thickness of SAH on axial CT and is predictive of vasospasm incidence. In this study, the authors further investigate whether different aneurysm locations result in different SAH clot burdens and whether any concurrent differences in ruptured aneurysm location and maximum SAH clot burden affect vasospasm incidence. Two hundred fifty patients who were part of a prospective randomized controlled trial were reviewed. Most outcome and demographic variables were included as part of the prospective randomized controlled trial. Additional variables were also collected at a later time, including vasospasm data and maximum clot thickness. Aneurysms were categorized into 1 of 6 groups: intradural internal carotid artery aneurysms, vertebral artery (VA) aneurysms (including the posterior inferior cerebellar artery), basilar trunk or basilar apex aneurysms, middle cerebral artery aneurysms, pericallosal aneurysms, and anterior communicating artery aneurysms. Twenty-nine patients with nonaneurysmal SAH were excluded. Patients with pericallosal aneurysms had the least average maximum clot burden (5.3 mm), compared with 6.4 mm for the group overall, but had the highest rate of symptomatic vasospasm (56% vs 22% overall, OR 4.9, RR 2.7, p = 0.026). Symptomatic vasospasm occurrence was tallied in patients with clinical deterioration attributable to delayed cerebral ischemia. There were no significant differences in maximum clot thickness between aneurysm sites. Middle cerebral artery aneurysms resulted in the thickest mean maximum clot (7.1 mm) but rates of symptomatic and radiographic vasospasm in this group were statistically no different compared with the overall group. Vertebral artery aneurysms had the worst 1-year modified Rankin scale (mRS) scores (3.0 vs 1.9 overall, respectively; p = 0.0249). A 1-year mRS score of 0-2 (good outcome) was found in 72% of patients overall, but in only 50% of those with pericallosal and VA aneurysms, and in 56% of those with basilar artery aneurysms (p = 0.0044). Patients with stroke from vasospasm had higher mean clot thickness (9.71 vs 6.15 mm, p = 0.004). The location of a ruptured aneurysm minimally affects the maximum thickness of the SAH clot but is predictive of symptomatic vasospasm or clinical deterioration from delayed cerebral ischemia in pericallosal aneurysms. The worst 1-year mRS outcomes in this cohort of patients were noted in those with posterior circulation aneurysms or pericallosal artery aneurysms. Patients experiencing stroke had higher mean clot burden.

Surgical and endovascular treatment for ruptured anterior circulation cerebral aneurysms: A comparison of outcomes – A single centre study from Taiwan

The purpose of this 2-year retrospective study is to compare the outcomes of patients with either surgical clipping or endovascular coiling treatment for ruptured anterior circulation cerebral aneurysms. We enrolled 100 patients with spontaneous subarachnoid hemorrhage resulting from ruptured anterior circulation cerebral aneurysms. We reviewed the demographic information, operative details, and image examinations including computed tomography (CT), digital subtraction angiography, and magnetic resonance imaging of brains. The patients were subdivided into two groups on the basis of treatment modalities: surgical clipping (N = 44) or endovascular coiling (N = 56). The modified Rankin's scale (mRS) was used as an outcome measures. Unfavorable outcome was defined by a mRS score of 1–3. The mean age of 100 patients, comprising 35 men and 65 women, was 57.48 ± 12.68 years. The follow-up period was 18.91 ± 13.05 months in average. The differences between the clipping and coiling groups in terms of admission Glasgow Coma Scale, Hunt and Hess grade, World Federation of Neurosurgical Societies grade, and Fisher's grade by CT scans were not statistically significant. There was no intergroup difference in the following results: symptomatic or radiographic vasospasm, post-treat rebleeding, and recurrence of aneurysms. Although the incidences of unfavorable outcome at the end of follow-up were 32.0% and 27.0% in the clipping and coiling group respectively, it revealed no significant difference (p = 0.202). In dealing with the patients with ruptured anterior circulation cerebral aneurysms, our results provide helpful information when discussing projected outcome before surgical or endovascular treatment.

Abstract WP427: Day Eight CT Perfusion Imaging for Evaluation of Delayed Cerebral Ischemia Risk and Decreased Length of Stay Following Aneurysmal Subarachnoid Hemorrhage

Objective: Hospital stay alone accounts for 2/3 the cost of aneurysmal subarachnoid hemorrhage (aSAH) management. Our objective was to assess the ability of CT perfusion (CTP) imaging to predict delayed cerebral ischemia (DCI) risk in those who are neurologically intact in order to safely decrease the length of hospital stay for low risk aSAH patients. Methods: A retrospective analysis of all aSAH admitted to our neurological intensive care unit (NICU) from 3/2011-3/2012. Per our protocol all patients were admitted to the NICU for 10 days followed by a 4 day ward admission. Additionally, all patients underwent a CTP study on post-bleed day 8 to screen for evidence of radiographic vasospasm. DCI was defined as the presence of neurological deficit not attributable to other etiologies. All CTP images were interpreted by a Neuroradiologist. CTP was considered positive if there was evidence of match or mismatch. Mismatch was defined as decreased cerebral blood flow or increased mean transit time with associated blood volume loss of <20%. Results: A total of 58 aSAH were admitted. Day 8 CTPs were performed on 42 (72%) with 71% female, mean age 52.21 (±13.25), mean Fisher 3.38 (2-4) and mean Hunt/Hess 2.39 (1-5). Eighteen (43%) patients had negative CTPs with baseline neurological exams. None of these 18 patients went on to develop DCI during their 14 day admission. Conclusion: Our data shows that aSAH patients who are neurologically intact and have a negative post-bleed day 8 CTP are not at risk for DCI. We conclude that an 8 day NICU admission with an additional 2 day in-patient stay is sufficient to safely manage this patient population. Our data is limited by a small sample size and retrospective analysis. Future directions of research include additional prospective studies for reproducibility.

Cerebral Vasospasm in Traumatic Brain Injury

Vasospasm following traumatic brain injury (TBI) may dramatically affect the neurological and functional recovery of a vulnerable patient population. While the reported incidence of traumatic vasospasm ranges from 19%–68%, the true incidence remains unknown due to variability in protocols for its detection. Only 3.9%–16.6% of patients exhibit clinical deficits. Compared to vasospasm resulting from aneurysmal SAH (aSAH), the onset occurs earlier and the duration is shorter. Overall, the clinical course tends to be milder, although extreme cases may occur. Traumatic vasospasm can occur in the absence of subarachnoid hemorrhage. Surveillance transcranial Doppler ultrasonography (TCD) has been utilized to monitor for radiographic vasospasm following TBI. However, effective treatment modalities remain limited. Hypertension and hypervolemia, the mainstays of treatment of vasospasm associated with aSAH, must be used judiciously in TBI patients, and calcium-channel blockers have offered mixed clinical results. Currently, the paucity of large prospective cohort studies and level-one data limits the ability to form evidence-based recommendations regarding the diagnosis and management of vasospasm associated with TBI.

Prophylactic magnesium for improving neurologic outcome after aneurysmal subarachnoid hemorrhage: Systematic review and meta-analysis

PurposeNeurologic disability is common after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to systematically review the prophylactic use of magnesium to improve neurologic outcomes in these patients. MethodsWe searched MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials to June 2012 for randomized and quasi-randomized controlled trials of intravenous magnesium in adults after aSAH, given before radiologic vasospasm or delayed cerebral ischemia (DCI) and compared with any control group. Two reviewers independently extracted data on study population, interventions, and outcomes (good neurologic outcome [primary outcome], cerebral infarction, DCI, radiographic vasospasm, mortality, adverse events). Analyses used random-effects models. ResultsOf 702 citations, 13 trials (n = 2401) met the selection criteria. Meta-analyses showed that magnesium did not increase the probability of good neurologic outcome (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97-1.07; P = .49; 12 trials, n = 2345) or decrease the risks of cerebral infarction (RR, 0.69; 95% CI, 0.46-1.05; P = .08; 5 trials, n = 572), radiographic vasospasm (RR, 0.86; 95% CI, 0.71-1.04; P = .13; 7 trials, n = 438), or mortality (RR, 0.98; 95% CI, 0.80-1.20; P = .86; 11 trials, n = 2092). Magnesium did reduce the risk of DCI (RR, 0.73; 95% CI, 0.56-0.96; P = .02; 10 trials, n = 1095). Data on adverse events were generally sparse. ConclusionsDespite decreasing the incidence of DCI in patients with aSAH, prophylactic intravenous magnesium does not improve neurologic outcome or decrease cerebral infarction, radiographic vasospasm, or mortality.

A Simple and Quantitative Method to Predict Symptomatic Vasospasm After Subarachnoid Hemorrhage Based on Computed Tomography

Although the Fisher scale is commonly used to grade vasospasm risk in aneurysmal subarachnoid hemorrhage (aSAH) patients, it fails to account for increasing subarachnoid hemorrhage (SAH) thickness. We developed a simple quantitative scale based on maximal SAH thickness and compared its reproducibility and ability to predict symptomatic vasospasm against the Fisher scale. The incidence of radiographic and symptomatic vasospasm among 250 aSAH patients treated at our institution was investigated. Admission head computed tomography scans were graded according to the Fisher scale and the proposed scale, which assigns a score from 1 to 5 based on a single measurement of maximum SAH thickness. We calculated vasospasm risk per grade for the Fisher scale and the proposed scale, and compared inter- and intraobserver variability for both scales. Forty-five patients (20.6%) developed symptomatic vasospasm. On the proposed scale, grade 5 patients were at highest risk, with an odds ratio for symptomatic vasospasm of 11 (95% confidence interval [CI] 2.27-53.37). Odds ratios for proposed grades 4 and 3 were 4.63 (95% CI 1.10-19.59) and 3.04 (95% CI 0.85-10.90), respectively. The odds ratio for Fisher grade 3 was 3.3 (0.96-11.30). Mean inter- and intraobserver agreement was greater for the proposed scale in comparison with the Fisher scale (κ0.65 and κ0.81 vs κ0.51 and κ0.35, respectively). The new scale accounted for increasing SAH thickness and was superior to the Fisher scale in inter- and intraobserver agreement and in predicting symptomatic vasospasm, particularly among the highest-risk patients.

Relationship between brain interstitial fluid tumor necrosis factor-α and cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Tumor necrosis factor-α (TNF-α) has a crucial role in the onset of hemolysis-induced vascular injury and cerebral vasoconstriction. We hypothesized that TNF-α measured from brain interstitial fluid would correlate with the severity of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH). From a consecutive series of 10 aSAH patients who underwent cerebral microdialysis (MD) and evaluation of vasospasm by CT angiogram (CTA) or digital subtraction angiography (DSA), TNF-α levels from MD were measured at 8-hour intervals from aSAH days 4–6 using enzyme-linked immunosorbent assay. An attending neuroradiologist blinded to the study independently evaluated each CTA and DSA and assigned a vasospasm index (VI). Five patients had a VI < 2 and 5 patients had a VI > 2, where the median VI was 2 (range 0–13). The median log TNF-α area under the curve (AUC) was 1.64 pg/mL ∗ day (interquartile range 1.48–1.71) for the VI < 2 group, and 2.11 pg/mL ∗ day (interquartile range 1.95–2.47) for the VI > 2 group (p < 0.01). Thus, in this small series of poor-grade aSAH patients, the AUC of TNF-α levels from aSAH days 4–6 correlates with the severity of radiographic vasospasm. Further analysis in a larger population is warranted based on our preliminary findings.

Pretruncal Nonaneurysmal Subarachnoid Hemorrhage Causing Basilar Artery Vasospasm

Pretruncal nonaneurysmal subarachnoid hemorrhage (PNSAH), more commonly known as perimesencephalic nonaneurysmal subarachnoid hemorrhage, is characterized by the presence of subarachnoid hemorrhage anterior to the midbrain with no evidence of an intracranial aneurysm on four vessel craniocervical angiogram. Although vasospasm is a common occurrence after aneurysmal subarachnoid hemorrhage and can lead to significant morbidity and mortality, vasospasm in the setting of PNSAH is rare. The purpose of this report is to describe the case of a patient with PNSAH who developed significant radiographic vasospasm of the basilar artery that altered clinical management. The current literature on this uncommon disease entity and management considerations are discussed. A four-vessel cerebral angiogram was performed on hospital day (HD) two that did not demonstrate any apparent vascular abnormality or vasospasm. A repeat craniocervical angiogram on HD 8 demonstrated significant stenosis of the basilar artery consistent with vasospasm. The patient continued to be neurologically intact. A repeat cerebral angiogram performed on HD 15 demonstrated resolving vasospasm. There continued to be no evidence of a source of his initial hemorrhage. PNSAH is associated with an excellent clinical course that is rarely associated with long-term sequelae. Although cerebral vasospasm rarely develops radiographically or clinically in patients with PNSAH, evidence suggests that clinical observation comparable to that performed in patients with aneurysmal SAH should be performed until a second confirmatory study has conclusively ruled out an aneurysmal source and until clinical and radiographic evidence of resolution of severe vasospasm is obtained.

Response to Letter by Vergouwen

Response: It has long been recognized that the relationship between angiographic vasospasm and “delayed neurological deficits” (DNDs) is imperfect.1 Some patients develop neurological deterioration despite no more than mild to moderate arterial narrowing. Others have impressive vasospasm without any symptoms. Delayed infarcts do not always occur in vascular territories with maximal vasospasm.2 Still, the proportion of patients who deteriorate without any radiographic vasospasm (and no other apparent cause such as hydrocephalus, seizures, or infection) is not well described. Given that approximately two thirds of total patients develop at least some angiographic vasospasm,1 and those who do not are often World Federation of Neurological Surgeons Grade 1 to 2 patients who are at low risk of DNDs, this probably represents a relatively small subset. In the Clazosentan to Overcome Neurological ischemia and Infarction Occurring …

Effect of Endothelin-Receptor Antagonists on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage Remains Unclear

To the Editor: With great interest I have read the recent meta-analysis on the effect of endothelin-receptor antagonists (ETRAs) in patients with aneurysmal subarachnoid hemorrhage.1 Because endothelin might have an important function in the pathogenesis of radiographic vasospasm, ETRAs are presently under intensive investigation in this group of patients. Recently, the results of a large double-blind, placebo-controlled Phase II study (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage [CONSCIOUS-1]) investigating the effect of the ETRA clazosentan in patients with aneurysmal subarachnoid hemorrhage for the first time revealed a 65% relative risk reduction (95% CI, 47% to 78%) of angiographically demonstrated vasospasm in the group of patients treated with the highest dose of clazosentan (15 mg/h).2 This finding was impressive, because no other drug ever before was found …

Do Endothelin-Receptor Antagonists Prevent Delayed Neurological Deficits and Poor Outcomes After Aneurysmal Subarachnoid Hemorrhage?

Delayed ischemic neurological deficits (DINDs) contribute to poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). Endothelin-1 is an important mediator involved in the development of vasospasm. We performed a systematic review and meta-analysis of randomized controlled trials assessing the use of endothelin-receptor antagonists (ETRAs) in patients with SAH. Three studies met eligibility criteria, enrolling 867 patients. ETRAs significantly reduced the occurrence of DINDs (OR 0.68 [0.49 to 0.95]) and radiographic vasospasm (OR 0.31 [0.19 to 0.49]), but did not have any impact on mortality (OR 1.09 [0.69 to 1.72]) or poor neurological outcomes (OR 0.87 [0.63 to 1.20]). Any benefit of ETRAs may have been partially offset by adverse effects, including hypotension(OR 2.39 [1.37 to 4.17]) and pulmonary complications (OR 2.12 [1.51 to 2.98]). Although ETRAs reduce radiographic vasospasm and DINDs, there is currently no evidence that they improve outcomes.

STATIN USE WAS NOT ASSOCIATED WITH LESS VASOSPASM OR IMPROVED OUTCOME AFTER SUBARACHNOID HEMORRHAGE

The development of delayed ischemia caused by cerebral vasospasm remains a common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Preliminary studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of vasospasm, but additional study is required. Beginning in May 2006, our treatment protocol for patients presenting with subarachnoid hemorrhage was altered to routinely include the use of 80 mg of simvastatin per day for 14 days. Before this time, only patients with other indications for statins were treated. The charts of 203 consecutive patients over a period of 27 months were retrospectively reviewed, and 150 patients were included in the analysis, of whom 71 patients received statins. These patients were compared with 79 untreated patients to determine whether or not the use of statins was associated with a reduction in the occurrence of vasospasm, delayed infarction, or poor outcome (death, vegetative state, or severe disability). Patients who were treated with statins and those who were not had similar baseline characteristics, although more patients in the former group were managed with endovascular coil embolization. There were no statistically significant differences in the proportion of patients developing at least moderate radiographic vasospasm (41% with statins versus 42% without, P = 0.91), symptomatic vasospasm (32% with statins versus 25% without, P = 0.34), delayed infarction (23% with statins versus 28% without, P = 0.46), or poor outcome (39% with statins versus 35% without, P = 0.61). After adjustment for differences in baseline characteristics, including the method of aneurysm treatment, statins were still not significantly protective. The addition of statins to standard care was not associated with any reduction in the development of vasospasm or improvement in outcomes after aneurysmal subarachnoid hemorrhage. If there is a benefit to statin use, it may be smaller than suggested by previous studies. However, further randomized controlled trials are awaited.

Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage

Vasospasm is one of the leading causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Radiographic vasospasm usually develops between 5 and 15 days after the initial hemorrhage, and is associated with clinically apparent delayed ischemic neurological deficits (DID) in one-third of patients. The pathophysiology of this reversible vasculopathy is not fully understood but appears to involve structural changes and biochemical alterations at the levels of the vascular endothelium and smooth muscle cells. Blood in the subarachnoid space is believed to trigger these changes. In addition, cerebral perfusion may be concurrently impaired by hypovolemia and impaired cerebral autoregulatory function. The combined effects of these processes can lead to reduction in cerebral blood flow so severe as to cause ischemia leading to infarction. Diagnosis is made by some combination of clinical, cerebral angiographic, and transcranial doppler ultrasonographic factors. Nimodipine, a calcium channel antagonist, is so far the only available therapy with proven benefit for reducing the impact of DID. Aggressive therapy combining hemodynamic augmentation, transluminal balloon angioplasty, and intra-arterial infusion of vasodilator drugs is, to varying degrees, usually implemented. A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists. This paper reviews established and emerging therapies for vasospasm.

Adrenoreceptor Polymorphisms and Subarachnoid Hemorrhage

See related article, pages 1680–1685. Neurogenic stunned myocardium (NSM) is reversible cardiac dysfunction, typically after subarachnoid hemorrhage (SAH).1,2 The most likely pathophysiology of NSM is a catecholamine surge that leads to transient ventricular dysfunction. The pathophysiology is probably similar to Tako-Tsubo cardiomyopathy3 and cardiac dysfunction caused by fright.4 SAH presents a different and acute clinical scenario, however, because these patients often require hyperdynamic therapy for symptomatic or radiographic vasospasm.5 Both increasing cardiac output and blood pressure increase cerebral perfusion,6 but hyperdynamic therapy with a failing left ventricle can quickly lead to pulmonary edema, hypoxia, hypotension and cerebral infarction.7 Methods to predict …

Simvastatin Reduces Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH. Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; n=19) or placebo (n=20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis. Serum markers of brain injury were recorded daily. The primary end point of vasospasm was defined as clinical impression (delayed ischemic deficit not associated with rebleed, infection, or hydrocephalus) in the presence of > or =1 confirmatory radiographic test (angiography or transcranial Doppler demonstrating mean V(MCA) >160 m/sec). There were no significant differences in laboratory-defined transaminitis or myositis between groups. No patients developed clinical symptoms of myopathy or hepatitis. Plasma von Willebrand factor and S100beta were decreased 3 to 10 days after SAH (P<0.05) in patients receiving simvastatin versus placebo. Highest mean middle cerebral artery transcranial Doppler velocities were significantly lower in the simvastatin-treated group (103+/-41 versus 149+/-47; P<0.01). In addition, vasospasm was significantly reduced (P<0.05) in the simvastatin-treated group (5 of 19) compared with those who received placebo (12 of 20). The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.