Angiographic Cerebral Vasospasm Research Articles

Analysis of Angiographic Treatment Response to Intra-Arterial Nimodipine Bolus Injection in Patients with Medically Refractory Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage

Intra-arterial nimodipine (IAN) injections are performed in refractory delayed cerebral ischemia (DCI) related to cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH), but the clinical benefits are inconclusive and angiographic treatment failure is observed. We analyzed angiographic IAN response in a detailed vessel-specific manner and examined the impact of poor angiographic response on the further clinical course. Clinical data were retrospectively assessed in patients with spontaneous subarachnoid hemorrhage with symptomatic CVS receiving IAN bolus treatment. Clinical and angiographic predictors for poor angiographic response, DCI-related infarction, and unfavorable outcome were analyzed. Eighty-nine patients were included and 356 treated vessel segments, mainly located in the anterior circulation (93%), were analyzed. Angiographic response was good in 77% of the treated segments. Older age, poor World Federation of Neurosurgical Societies (WFNS) grade 4-5 and early onset of CVS were independently associated with poor angiographic response. The factors short-segment, distal, and bilateral CVS as well as treatment of multiple vessel segments, WFNS grade 4-5, and early onset of CVS were significantly associated with an increased risk of DCI-related infarction. Clinical outcome was significantly influenced by poor WFNS grade and early onset of CVS, whereas poor angiographic response was not related to DCI-related infarction or unfavorable outcome. The risk of angiographic treatment failure is significantly increased in older patients and those with poor WFNS grade as in cases of early-onset CVS. Although the extent of angiographic CVS significantly affected the development of DCI-related infarction, poor angiographic response had no impact on cerebral infarction and clinical outcome.

Electroencephalography for detection of vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective analysis and systematic review.

Good functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH) are often dependent on early detection and treatment of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI). There is growing evidence that continuous monitoring with cranial electroencephalography (cEEG) can predict CVS and DCI. Therefore, the authors sought to assess the value of continuous cEEG monitoring for the detection of CVS and DCI in aSAH. The cerebrovascular database of a quaternary center was reviewed for patients with aSAH and cEEG monitoring between January 1, 2017, and July 31, 2019. Demographic data, cardiovascular risk factors, Glasgow Coma Scale score at admission, aneurysm characteristics, and outcomes were abstracted from the medical record. Patient data were retrospectively analyzed for DCI and angiographically assessed CVS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and odds ratio for cEEG, transcranial Doppler ultrasonography (TCDS), CTA, and DSA in detecting DCI and angiographic CVS were calculated. A systematic literature review was conducted in accordance with PRISMA guidelines querying the PubMed, Cochrane Controlled Trials Register, Web of Science, and Embase databases. A total of 77 patients (mean age 60 years [SD 15 years]; female sex, n = 54) were included in the study. Continuous cEEG monitoring detected DCI and angiographically assessed CVS with specificities of 82.9% (95% CI 66.4%-93.4%) and 94.4% (95% CI 72.7%-99.9%), respectively. The sensitivities were 11.1% (95% CI 3.1%-26.1%) for DCI (n = 71) and 18.8% (95% CI 7.2%-36.4%) for angiographically assessed CVS (n = 50). Furthermore, TCDS detected angiographically determined CVS with a sensitivity of 87.5% (95% CI 71.0%-96.5%) and specificity of 25.0% (95% CI 7.3%-52.4%). In patients with DCI, TCDS detected vasospasm with a sensitivity of 85.7% (95% CI 69.7%-95.2%) and a specificity of 18.8% (95% CI 7.2%-36.4%). DSA detected vasospasm with a sensitivity of 73.9% (95% CI 51.6%-89.8%) and a specificity of 47.8% (95% CI 26.8%-69.4%). The study results suggest that continuous cEEG monitoring is highly specific in detecting DCI as well as angiographically assessed CVS. More prospective studies with predetermined thresholds and endpoints are needed to assess the predictive role of cEEG in aSAH.

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

Background and purposeDelayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage.MethodsThe CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI‐DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut‐off scores. Inter‐rater reliability was evaluated by Cohen's kappa coefficient.ResultsThis study included 59 patients. CI‐DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI‐)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI‐DCI 0.89 (95% confidence interval [CI] 0.79–0.99), DCI 0.68 (95% CI 0.50–0.87) and functional outcome 0.74 (95% CI 0.57–0.91). Cohen's kappa between the two raters was moderate to substantial (0.57–0.63).ConclusionsThis study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI‐)DCI and unfavorable outcome.

Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

Platelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

A case report on the management of severe vasospasm in subarachnoid hemorrhagic patients using intra-arterial nimodipine, intrathecal sodium nitroprusside and intra-arterial papaverine

Management and prevention of vasospasm in subarachnoid haemorrhage are one of the complex dictums so far. Aneurysmal subarachnoid haemorrhage (aSAH) is the condition in which bleeding occurs in subarachnoid space. Vasospasm is a complex immunologically active phenomenon which requires a multimodality approach in the treatment of established vasospasm. Various treatment strategies for vasospasm and related disabilities include vasodilators such as nimodipine, sodium nitroprusside and papaverine. Intra-arterial nimodipine shows drastic improvement in several patients by resolving and preventing vasospasm. Intra-arterial administration of nimodipine can cause hypotension which can be easily managed. Papaverine is also an efficient drug-producing vasodilatory action on cerebral arteries. Papaverine is considered as the first intraarterial agent to reduce angiographic cerebral vasospasm which has the side effect of elevated intracranial pressure. Besides, the intrathecal administration of sodium nitroprusside has also demonstrated the effect in ischemic vasospasm after subarachnoid haemorrhage. Intraarterial administration of this drug can induce arterial hypotension which is not a recommended method. Vomiting is the main side effect of sodium nitroprusside, which can be managed with antiemetics such as ondansetron. Here we present a case of management of cerebral vasospasm in subarachnoid patients using the combination of these three effective drugs which showed a remarkable improvement in the resolution of aneurysmal vasospasm.

Computed tomography perfusion imaging after aneurysmal subarachnoid hemorrhage can detect cerebral vasospasm and predict delayed cerebral ischemia after endovascular treatment.

Background: Endovascular treatment (ET) can improve angiographic cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage, but was unrelated to clinical outcomes in previous analyses. Appropriate detection of CV and precise indications for ET are required. This study investigated whether changes in computed tomography perfusion (CTP) parameter can determine indications for ET in CV and predict its effectiveness.Methods: Participants comprised 140 patients who underwent neck clipping or coil embolization. CTP was performed a week after aneurysmal treatment or when clinical deterioration had occurred. Patients were divided into ET and non-ET groups by propensity score matching. In addition, the ET group was divided into subgroups with and without new cerebral infarction (CI). All CTP images in the three groups were retrospectively investigated qualitatively and quantitatively. CI was diagnosed from CT at 3 months postoperatively.Results: Of the 121 patients examined, 15 patients (11%) needed ET. In qualitative analysis, all ET group patients displayed extension of time-to-peak (TTP) at the region of vasospastic change, regardless of the presence of CI. Quantitative analysis showed significant decreases in cerebral blood volume (P < 0.01), cerebral blood flow (CBF) (P < 0.001), and extension in TTP (P < 0.01) in the ET group compared with the non-ET group. A significant decrease in CBF (P < 0.001) and extension in mean transit time (P < 0.001) was seen in the ET with CI subgroup compared with the ET without CI subgroup.Conclusion: CTP in the vasospastic period may be an indication for ET and predict the effectiveness of ET for CV to improve clinical outcomes.

Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage: Angiographic Pattern and Its Impact on the Clinical Course

To analyze angiographic characteristics of cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH) and their potential impact on secondary infarction and functional outcome. Demographic, clinical, and imaging data of sSAH patients with angiographic CVS admitted over a 6-year period were retrospectively analyzed. A total of 85 patients were included in the final analysis. A total of 311 arterial territories in 85 angiographies demonstrated angiographic CVS. The anterior cerebral artery (ACA) was the most common site of angiographic CVS (42.1%), followed by the middle cerebral artery (MCA) (26.7%). In 29 angiographies (34%) CVS was found in more than 3 vessels and a bilateral pattern was identified in 53 cases (62%). Older age (OR 3.24 [95% CI 1.30-8.07], P= 0.012) was identified as the only significant risk factor for CVS-related infarction (OR 22.67, P= 0.015). Unfavorable outcome was associated with older age (OR 3.24, P= 0.023) and poor World Federation of Neurosurgical Societies grade (OR 3.64, P= 0.015). Analyses of angiographic characteristics did not reveal any risk factors for unfavorable outcome. We identified distal CVS as a significant risk factor for CVS-related infarction (OR 2.89, P= 0.026). Angiographic CVS after sSAH shows a specific distribution pattern in favor of ACA and MCA and in most cases 2-3 affected vessels are affected, often bilaterally. Patients exhibiting distal CVS have a higher risk for CVS-related infarction and should be observed closely. Nonetheless, the majority of angiographic characteristics did not allow conclusions about functional outcome nor the occurrence of CVS-related infarction in sSAH patients.

Abstract TP463: Treatment of Asymptomatic Angiographic Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage May Prevent Progression to Delayed Cerebral Ischemia

Objective: Endovascular treatment of angiographic cerebral arterial vasospasm (CVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH), who do not fulfill criteria for delayed cerebral ischemia (DCI), remains controversial. We sought to investigate the relationship of endovascular intervention with the development of DCI. Method: Consecutive patients admitted between 2017 and 2019 with aSAH were analyzed retrospectively. Rates of development of DCI were compared between two groups - the treated group: patients not in DCI who underwent conventional digital subtraction angiography (DSA) between days 3 and 14 of ictus and were treated endovascularly for CVS, - the untreated group: patients who did not undergo DSA or did get DSA but did not receive endovascular treatment for CVS. Pearson’s chi-square test for independence was used to compare progression to DCI and t-test for independent samples was used to compare modified fisher scale (mFS) among the 2 groups. Multivariate logistic regression using stepwise backward selection was used to evaluate the predictors of DCI. Results: A total of 83 patients were analyzed. 21 patients (25%) were treated for angiographic vasospasm. 70% of these patients had moderate or severe CVS. 15 (15%) underwent DSA but were not treated angiographically. DSA was performed on an average of day 8 [5-12] post-ictus. 47 (57%) did not received DSA. Although, patients treated for angiographic CVS had higher modified Fisher Scale mFS (p=0.11), the rate of progression to DCI was higher among the untreated group 20 (32%) compared to the treated group (10%) (p =0.04). Delayed cerebral ischemia occurred at an average of day 6 [2-16] post-ictus. Although 15 out of 36 (42%) had DSA but were untreated due to absence or visualization of non-significant CVS, the treated group (68%) had significantly higher mFS (p=0.02) and elevated TCD velocities (p=0.03). mFS (p=0.04) and lack of past medical history of hypertension (p=0.03) were predictors of DCI. Conclusion: Endovascular treatment of angiographic CVS in asymptomatic patients was associated with lower risk of progression to DCI. A large prospective study is needed to evaluate its potential to prevent progression to DCI in high risk patients.

Neuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a sub-type of hemorrhagic stroke associated with the highest rates of mortality and long-term neurological disabilities. Despite the improvement in the management of SAH patients and the reduction in case fatality in the last decades, disability and mortality remain high in this population. Brain injury can occur immediately and in the first days after SAH. This early brain injury can be due to physical effects on the brain such as increased intracranial pressure, herniations, intracerebral, intraventricular hemorrhage, and hydrocephalus. After the first 3 days, angiographic cerebral vasospasm (ACV) is a common neurological complication that in severe cases can lead to delayed cerebral ischemia and cerebral infarction. Consequently, the prevention and treatment of ACV continue to be a major goal. However, most treatments for ACV are vasodilators since ACV is due to arterial vasoconstriction. Other targets also have included those directed at the underlying biochemical mechanisms of brain injury such as inflammation and either independently or as a consequence, cerebral microthrombosis, cortical spreading ischemia, blood–brain barrier breakdown, and cerebral ischemia. Unfortunately, no pharmacologic treatment directed at these processes has yet shown efficacy in SAH. Enteral nimodipine and the endovascular treatment of the culprit aneurysm, remain the only treatment options supported by evidence from randomized clinical trials to improve patients’ outcome. Currently, there is no intervention directly developed and approved to target neuroinflammation after SAH. The goal of this review is to provide an overview on anti-inflammatory drugs tested after aneurysmal SAH.

ω-3 Fatty Acids Ethyl Esters Suppress Cerebral Vasospasm and Improve Clinical Outcome Following Aneurysmal Subarachnoid Hemorrhage.

Occurrence of cerebral vasospasm after onset of aneurysmal subarachnoid hemorrhage (SAH) is a critical factor determining clinical prognosis. Eicosapentaenoic acid and docosahexaenoic acid, both ω-3 fatty acids (ω-3FA), can suppress cerebral vasospasm, and docosahexaenoic acid can relax vessel vasoconstriction and have neuroprotective effects. We investigated whether administration of ω-3FA prevented cerebral vasospasm occurrence and improved clinical outcomes after aneurysmal SAH. From 2012 to 2015, 100 consecutive patients with aneurysmal SAH were divided into 2 periods. Between 2012 and 2013 (control period), 45 patients received standard management. Between 2014 and 2015 (ω-3FA period), 55 patients were prospectively treated with additional ω-3FA. Occurrence of cerebral vasospasm, occurrence of cerebral infarction caused by vasospasm, and modified Rankin Scale scores at 30 days and 90 days after onset of SAH for each period were evaluated and compared. The frequency of angiographic cerebral vasospasm in the ω-3FA period was significantly lower than in the control period (12 patients vs. 23 patients, P=0.004). The frequency of new infarction caused by vasospasm in the ω-3FA period was also significantly lower than in the control period (5 patients vs. 14 patients, P= 0.011). There was a significant difference in modified Rankin Scale scores at 90 days after onset of SAH between the groups (P= 0.031). No adverse events were associated with ω-3FA administration. Administration of ω-3FA after aneurysmal SAH may reduce the frequency of cerebral vasospasm and may improve clinical outcomes.

The role of spreading depolarization in subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating disease associated with death and poor functional outcome. Despite decades of intense research and improvements in clinical management, delayed cerebral ischaemia (DCI) remains the most important cause of morbidity and mortality after SAH. The key role of angiographic cerebral vasospasm, thought to be the main cause of DCI, has been questioned. Emerging evidence suggests that DCI is likely to have a multifactorial etiology. Over the last few years, spreading depolarization (SD) has been identified as a potential pathophysiological mechanism contributing to DCI. The presence of cortical spreading ischaemia, due to an inverse hemodynamic response to SD, offers a possible explanation for DCI and requires more intensive research. Understanding the role of SD as another mechanism inducing DCI and its relationship with other pathological factors could instigate the development of new approaches to the diagnosis and treatment of DCI in order to improve the clinical outcome.

Beyond Delayed Cerebral Vasospasm: Infarct Patterns in Patients with Subarachnoid Hemorrhage

Angiographic vasospasm (CVS) has been accused to be the main cause of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, treatment success including endovascular treatment remains to be improved. We performed a pattern analysis of ischemic lesions in SAH patients in the absence of angiographic cerebral vasospasm to generate further hypotheses concerning etiology and risk factors of DCI apart from vasospastic narrowing. We retrospectively included 309 patients with cerebral infarcts after SAH. Vasospasm was assessed by means of CT or MR angiography and perfusion measurement or digital subtraction angiography. All clinical and radiological data were used to determine the most probable etiology for new infarcts. Twenty-seven percent of patients showed infarcts without presence of angiographic vasospasm. Seventy-three percent of these "atypical infarcts" were induced by complications of aneurysm therapy, 7 % by hypoxia, 2 % by ICP-related herniation. In 17 %, the etiology remained unclear; however, disturbances of the microcirculation for different reasons were the most likely cause in these patients. Beyond CVS and treatment complications, a not insignificant number of SAH patients suffered from infarcts of other etiology probably due to disturbance of the microcirculation. Therapeutic approaches for vasodilation of angiographic vasospasm alone should be reconsidered.

Abstract 4037: Dynamic Cerebral Autoregulation in Patients with Subarachnoid Hemorrhage and Delayed Cerebral Ischemia

Introduction: We have previously shown that early impairments in dynamic cerebral autoregulation are strongly associated with subsequent development of angiographic cerebral vasospasm. While angiographic cerebral vasospasm is associated with delayed cerebral ischemia (DCI), the relationship between cerebral autoregulation and DCI has not been previously investigated. Our study is designed to specifically test the relationship between early changes in dynamic cerebral autoregulation and subsequent development of DCI. Methods: Thirty-nine consecutive patients with acute non-traumatic subarachnoid hemorrhage (SAH) and adequate transcranial Doppler windows, presenting within 24 hours of symptom onset, have been prospectively studied so far. Daily 5-minute measures of continuous beat-to-beat bilateral middle cerebral artery (MCA) flow velocity and mean arterial blood pressure (MAP) recordings were obtained on days 1-10. Transfer function analysis of spontaneous MAP and MCA mean flow velocity (MFV) oscillations were performed in the very low (0.03-0.07 Hz), low (0.07-0.15 Hz), and high (0.15-0.3 Hz) frequency ranges. Non contrast head CTs were reviewed by a neurologist and neuroradiologist blinded to the autoregulatory and angiographic data. Infarctions present within 6 weeks after SAH, which could not be attributed to instrumentation or peri-op strokes, were identified as DCI. Results: Patients with DCI had significantly higher Hunt and Hess (H&amp;H) scores (median=4 vs 3, p&lt;0.0001) compared to those without DCI. There was no difference in MAP (p=0.746), right MCA (p=0.8327)) or left MCA MFV (p=0.4278) between patients with and without DCI across all time points. Patients with DCI had a lower transfer function phase in the very low frequency (autoregulatory frequency) range. Subgroup analysis of patients with H&amp;H scores ≥3 (N=14) showed that those with DCI had significantly lower phases on day 3 compared to those without DCI (-13±80 vs. 63±26, p=0.048). Conclusion: Our preliminary data show that dynamic cerebral autoregulation, as measured by transfer function phase in the autoregulatory frequency range, is significantly impaired in the early days after SAH and that this early impairment is associated with the development of DCI. We are continuing to collect data on additional patients with SAH to confirm our findings in a larger cohort. Impairments in dynamic cerebral in the early days post SAH may be reliable predictors for identifying patients at higher risk of delayed cerebral ischemia.

Improvement in Angiographic Cerebral Vasospasm after Intra-Arterial Verapamil Administration

Endovascular options for therapy for patients with vasospasm after SAH include angioplasty and intra-arterial vasodilator infusion. Preliminary studies of the effects of the calcium channel antagonist verapamil on angiographic vasospasm have yielded mixed and/or qualitative results. In this study, improvement in angiographic vasospasm after intra-arterial verapamil administration is demonstrated with quantitative, blinded methods. This retrospective observational case series includes 12 patients with vasospasm after SAH who collectively received 16 treatments with intra-arterial verapamil during a 2-year period at our institution. The exclusion criterion was concurrent treatment with angioplasty. Blinded reviewers quantitatively evaluated angiograms from each patient and/or treatment after presentation with SAH and before and after intra-arterial treatment of vasospasm. Patients were treated with intra-arterial verapamil for vasospasm 9 ± 4 days after SAH with a range from 1 to 16 days. For the 34 arterial distributions treated, the segment with the worst angiographic vasospasm from each arterial distribution averaged 51 ± 13% stenosis, which improved to 29 ± 18% stenosis (P < .001). There was no significant difference in treatment effect in proximal arterial segments, which may be amenable to angioplasty, compared with distal segments (P > .05). There was no significant difference in treatment effect in arterial segments previously subjected to angioplasty compared with other segments (P > .05). Intra-arterially administered verapamil improves angiographic vasospasm after SAH when administered at 10 ± 3 mg per arterial distribution. Optimal dose, infusion rate, and retreatment interval remain to be determined. Randomized controlled trials are needed to prove efficacy in the treatment of clinical vasospasm.

Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH

The relation between angiographically determined cerebral vasospasm following a subarachnoid hemorrhage and regional cerebral blood flow (CBF) was studied in 63 investigations of 45 patients. The CBF was measured using the intra-arterial 133-Xe clearance technique within one hour of angiography. A positive correlation between regional CBF and diameter of major supplying vessel was observed. However, in the 13 cases with focal vasospasm the reduction in CBF was global and not restricted to the area of the spastic vessel. The cerebral oxygen extraction was reduced but independent of the degree of vasospasm, speaking against vasospasm as the cause for the reduction in CBF. The observed association between reduction in CBF and vasospasms could be caused by a common factor responsible for development of both. Thus, it is proposed that the amount of blood escaping at time of aneurysm rupture determines 1) the amount of reduction in cerebral oxygen uptake and thereby the reduction in CBF and 2) the degree of vasospasm. If so a correlation, yet not causal, between reduction in CBF and degree of vasospasm, will be observed.

Near-complete resolution of angiographic cerebral vasospasm after extreme elevation of mean arterial pressure: case report

Background Cerebral vasospasm is a widespread and potentially treatable complication after aneurysmal SAH. Aggressive treatment often includes hemodynamic augmentation, although the exact mechanism by which such therapy leads to improved cerebral blood flow and reduced neurologic deficits is incompletely established. This case report is only the second to provide compelling evidence that hypertension can lead to direct dilation of vasospastic arteries, thereby providing valuable insight into its potential mechanism. Case Description We present a patient with SAH from a ruptured anterior communicating artery aneurysm who developed marked decline in mental status on posthemorrhage day 11, consistent with symptomatic cerebral vasospasm. A diagnostic cerebral angiogram was performed demonstrating extensive and diffuse cerebral vasospasm. After receiving a nonselective slow infusion of verapamil, the patient developed an episode of extreme hypertension. Repeat angiography immediately after hypertensive crisis revealed near-complete resolution of the previously noted cerebral vasospasm. Rapid improvement in the patient's neurologic status ensued. Conclusion The present case illustrates that extreme hypertension can lead to direct dilation of vasospastic arteries and suggests that hypertensive-type hemodynamic therapy may act not only through increasing the pressure gradient across vasospastic arteries but also via direct induction of arterial vasodilation.

Effects of the selective endothelin A (ETA) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage – preliminary results from a randomized clinical series

To study the effects of clazosentan, a new selective endothelin receptor subtype A antagonist, on cerebral perfusion and cerebral oxygenation following severe aneurysmal subarachnoid haemorrhage (aSAH). All 12 patients treated at our institution in the context of a phase IIa, multicenter, randomized trial on clazosentan's safety and efficacy in reducing the incidence of angiographic cerebral vasospasm were included in this substudy. The phase IIa study (n = 34) consisted of two parts: a double-blind, randomized Part A (clazosentan 0.2 mg/kg/h versus placebo) and an open-label Part B (clazosentan 0.4 mg/kg/h for 12 h followed by 0.2 mg/kg/h) for patients with established vasospasm. In parallel to the phase IIa study protocol, which included assessment of vasospasm by angiography and transcranial Doppler sonography, we determined regional cerebral blood flow (rCBF), cerebrovascular resistance, and regional tissue oxygenation. Cerebral perfusion was comparable between treatment groups during the early post-bleeding period (rCBF placebo, 22.6 +/- 3.5 ml/100 g/min versus rCBF clazosentan, 23.9 +/- 1.1 ml/100 g/min). By the time of control angiography (day 8 after aSAH), rCBF decreased by 50% in the placebo group (11.3 +/- 6.7 ml/ 100 g/min) while it remained stable in the clazosentan group (23.5 +/- 12.9 ml/100 g/min). During Part B of the study, all 3 patients who developed haemodynamically relevant vasospasm during placebo treatment, showed a sustained improvement in rCBF upon conversion to clazosentan. These preliminary data suggest that clazosentan reduces the extent of vasospasm-associated impairment of cerebral perfusion following aSAH. Furthermore, clazosentan may exert beneficial actions on overt vasospasm-associated hypoperfusion.

Impairment of Cerebral Perfusion and Infarct Patterns Attributable to Vasospasm After Aneurysmal Subarachnoid Hemorrhage

The objective of this study was to investigate disturbance of perfusion and infarct patterns attributable to cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). One hundred seventeen patients with aneurysmal SAH specifically selected at high risk for CVS were enrolled in this prospective study. One hundred twelve patients underwent surgical (n=63) or endovascular (n=59) therapy. For assessment of CVS, relative diameter changes of proximal and distal vessel segments on follow-up angiography at day 7+/-3 after SAH were analyzed in relation to baseline measurements, and cerebral circulation times were measured. Postprocedure MRI was undertaken selectively at four time points: within 3 days, between days 4 and 6, day 7 to 14, and day 15 to 28 from onset of SAH, including perfusion- and diffusion-weighted images. Procedure-related lesions were excluded and CVS-associated infarct patterns analyzed. Occurrence of angiographic CVS was as high as 87.5% between days 7 and 14 and 52.5% showed new infarcts. Eighty-one percent of the infarcts were related to severe CVS (vascular narrowing >66%) and significant (P<0.001) cerebral circulation times prolongation of 8.47+/-2.25 seconds (time-to-peak delay on perfusion-weighted image: 6.52+/-4.75 seconds), 16% were associated with moderate CVS (34% to 66% vascular narrowing; cerebral circulation times prolongation: 4.72+/-0.66 seconds). Besides territorial (47%), lacunar (20%), and watershed infarcts (26%), in 7%, band-like cortical lesions developed without evidence for severe CVS. CVS after SAH may involve the complete arterial system from the circle of Willis up to the distal vessel segments. Depending on the variable types of collateral flow, location of affected vessels segments as well as the degree of CVS may induce different infarct patterns.

Biomechanical and phenotypic changes in the vasospastic canine basilar artery after subarachnoid hemorrhage

Because it has been argued that active myogenic tone prolongs cerebral vasospasm for >2 wk after subarachnoid hemorrhage (SAH), we attempted to identify the mechanism that plays the main role in sustaining the prolonged cerebral vasospasm. We especially focused on the roles of biomechanical and phenotypic changes in the cerebral arteries in the mechanisms of prolonged vasospasm after SAH. We used the basilar arteries from a "two-hemorrhage" canine model to make serial measurements of maximal contraction capacity and arterial stiffness (papaverine-insensitive tone) until day 28. We also examined hematoxylin-eosin-stained vasospastic canine basilar arteries for histological changes and immunohistochemically examined them for expression of myosin heavy chain isoforms (SMemb, SM1, and SM2), which are markers of smooth muscle phenotypic changes. Changes in collagen concentration in canine basilar arteries were also measured. Angiographic cerebral vasospasm persisted until day 14 and then gradually diminished; artery diameter returned to the control diameters on day 28. Maximal contraction capacity decreased until day 21 and showed some recovery by day 28. Arterial stiffness, on the other hand, progressed until day 28. Histological examination revealed medial thickening and increased connective tissue until day 21 and a return to control findings by day 28. The increased connective tissue was not accompanied by changes in collagen concentration, suggesting a role of some other protein in the increase in connective tissue. Immunohistochemical studies with anti-SMemb, anti-SM1, and anti-SM2 antibodies showed enhanced expression of SMemb from day 7 to day 21 and disappearance of SM1 and SM2 on days 14 and 21. The changes in myosin heavy chain isoform expression returned to normal on day 28. The above results indicate that biomechanical and phenotypic changes may play a pivotal role in sustaining cerebral vasospasm for >2 wk after SAH, with minimal changes in active myogenic arterial tone.

Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Background Plasma and cerebrospinal fluid (CSF) concentrations of endothelin-1 (ET-1) were measured in patients with subarachnoid hemorrhage (SAH) after aneurysmal rupture and compared with levels of ET-1 in volunteers. We analyze the relationship between levels of ET-1 in both CSF and plasma with the risk of developing cerebral vasospasm (CVS). Methods Cerebrospinal fluid and blood samples were collected from 30 selected patients after SAH and from 10 healthy volunteers who were used as control. All samples were stored at −70°C and the levels of ET-1 in CSF and blood were measured by using enzyme-linked immunosorbent assay and Western blot. All patients were submitted to angiography to confirm vasospasm. Results From the 30 patients admitted at different days of SAH, 18 (60%) developed clinical CVS and 10 (33%) presented angiographic CVS. The levels of ET-1 in the CSF were significantly higher ( P = .0001) in patients (1.618 ± 1.05 fmol/mL) than in controls (0.365 ± 0.328 fmol/mL). There was statistical difference ( P < .05) in CSF levels of ET-1 between each group of the Hunt-Hess scale and controls. The mean plasma concentration of ET-1 was similar ( P > .05) in the control group (1.531 ± 0.753 fmol/mL) and in patients with SAH (1.920 ± 1.15 fmol/mL). Conclusions These findings indicate that a significant rise in ET-1 levels in the CSF, but not in the plasma, occurs in patients who develop CVS after SAH. Our observation suggests that ET-1 might be involved in the pathogenesis of SAH-associated CVS.