Severe Angiographic Vasospasm Research Articles

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options. To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH. This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated. During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group). The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography. Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups. These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted. ClinicalTrials.gov Identifier: NCT04269408.

HummingFlow: novel single twist-drill access for ventricular drainage, irrigation, monitoring, and automated local drug delivery in subarachnoid hemorrhage.

The management of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) remains one of the most important targets for neurocritical care. Advances in monitoring technology have facilitated a more thorough understanding of the pathophysiology and therapeutic approaches, but interventions are generally limited to either systemic therapies or passive CSF drainage. The authors present a novel approach that combines a multimodal monitoring bolt-based system with an irrigating ventricular drain capable of delivering intrathecal medications and describe their early experience in patients with aSAH. The authors performed a retrospective review of cases treated with the combined Hummingbird multimodal bolt system and the IRRAflow irrigating ventriculostomy. Nine patients were treated with the combined multimodal bolt system with irrigating ventriculostomy approach. The median number of days to clearance of the third and fourth ventricles was 3 days in patients with obstructive intraventricular hemorrhage. Two patients received intrathecal alteplase for intraventricular hemorrhage clearance, and 2 patients received intrathecal nicardipine as rescue therapy for severe symptomatic angiographic vasospasm. Combined CSF drainage, irrigation, multimodality monitoring, and automated local drug delivery are feasible using a single twist-drill hole device. Further investigation of irrigation settings and treatment approaches in high-risk cases is warranted.

Walk-In Hospital Admission of Patients with Subarachnoid Hemorrhage: Clinical Presentation and Outcome

Neurosurgeons occasionally encounter cases of subarachnoid hemorrhage (SAH) in admitted walk-in patients, termed "walk-in SAH." However, their clinical characteristics have not been fully understood. We thus, aimed to investigate several characteristics of patients with walk-in SAH and compare them with those of patients with good grade SAH who arrived at the hospital by ambulance. Between January 2011 and January 2018, consecutive patients with World Federation of Neurosurgical Society (WFNS) grade I and II aneurysmal SAH were enrolled. They were dichotomized into walk-in and ambulance groups, and their demographic and disease-related characteristics were compared. Furthermore, predictors associated with unfavorable outcomes were investigated in patients with walk-in SAH. Of 171 patients with World Federation of Neurosurgical Society grade I and II SAH, 68 (39.8%) were categorized as walk-in SAH. The mean time for diagnosis in patients with walk-in SAH was significantly longer than that in patients who arrived by ambulance (P < 0.01). Multivariate analysis demonstrated that a lower rate of hypertension, high grades on the Barrow Neurological Institute scale, and Early Brain Edema Score were significantly associated with walk-in SAH (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.21-0.91, P= 0.03; OR 0.32, 95% CI 0.13-0.76, P= 0.007; OR 0.11, 95% CI 0.02-0.51, P < 0.0001, respectively). Additionally, severe angiographic vasospasm was a significant predictor of unfavorable outcomes in walk-in SAH (OR 37.7, 95% CI 1.10-1290.90, P= 0.04). Patients with walk-in SAH exhibit radiological characteristics associated with a more favorable outcome among patients with good grade SAH. Therefore, these patients may have a positive prognosis.

Vasospasm secondary to responsive neurostimulator placement: a previously unreported complication. Illustrative case.

The Responsive Neurostimulation (RNS) system is an implantable device for patients with drug-resistant epilepsy who are not candidates for resection of a seizure focus. As a relatively new therapeutic, the full spectrum of adverse effects has yet to be determined. A literature review revealed no previous reports of cerebral vasospasm following RNS implantation. A 35-year-old man developed severe angiographic and clinical vasospasm following bilateral mesial temporal lobe RNS implantation. He initially presented with concerns for status epilepticus 8 days after implantation. On hospital day 3, a decline in his clinical examination prompted imaging studies that revealed a left middle cerebral artery (MCA) stroke with angiographic evidence of severe vasospasm of the left internal carotid artery (ICA), MCA, anterior cerebral artery (ACA), and right ICA and ACA. Despite improvements in angiographic vasospasm after appropriate treatment, a thrombus developed in the posterior M2 branch, requiring mechanical thrombectomy. Ultimately, the patient was stabilized and discharged to a rehabilitation facility with residual cognitive and motor deficits. Cerebral vasospasm as a cause of ischemic stroke after uneventful RNS implantation is exceedingly rare, yet demands particular attention given the potential for severe consequences and the growing number of patients receiving RNS devices.

Cilostazol Administration for Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials.

The efficacy of cilostazol administration to treat subarachnoid hemorrhage remains controversial. We conduct a systematic review and meta-analysis to explore the influence of cilostazol administration on treatment efficacy for subarachnoid hemorrhage. We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases through July 2020 for randomized controlled trials assessing the effect of cilostazol administration in patients with subarachnoid hemorrhage. This meta-analysis is performed using the random-effect model. Four randomized controlled trials involving 405 patients were included in the meta-analysis. Overall, compared with control group for subarachnoid hemorrhage, cilostazol intervention can significantly reduce symptomatic vasospasm (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.21-0.60; P = 0.0001) and cerebral infarction (OR, 0.40; 95% CI, 0.22-0.73; P = 0.003) and improve no or mild angiographic vasospasm (OR, 2.01; 95% CI, 1.19-3.42; P = 0.01) and an mRS score of 2 or less (OR, 2.70; 95% CI, 1.09-6.71; P = 0.03), but revealed no obvious influence on severe angiographic vasospasm (OR, 0.53; 95% CI, 0.27-1.02; P = 0.06). There were no increase in adverse events (OR, 1.17; 95% CI, 0.54-2.52; P = 0.69), hemorrhagic events (OR, 0.62; 95% CI, 0.06-6.27; P = 0.69), and cardiac events (OR, 2.14; 95% CI, 0.44-10.27; P = 0.34) after the cilostazol intervention than control intervention. Cilostazol treatment may be effective to treat subarachnoid hemorrhage in the terms of symptomatic vasospasm, cerebral infarction, no or mild angiographic vasospasm, and an mRS score of 2 or less.

Cilostazol for Aneurysmal Subarachnoid Hemorrhage: An Updated Systematic Review and Meta-Analysis

Background and Purpose: Delayed cerebral ischemia is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Cilostazol, a selective inhibitor of phosphodiesterase 3, was reported to reduce cerebral vasospasm and improve outcomes. We aimed to conduct an updated systematic review and meta-analysis of the efficacy and safety of cilostazol in aSAH. Methods: We systematically searched PubMed, Embase, MEDLINE, and the Cochrane Library for articles published in English with the latest publishing time in August 2020. Articles reporting favorable outcome as the primary outcome and reporting severe angiographic vasospasm (aVS), symptomatic vasospasm (sVS), new cerebral infarction, or mortality as the secondary outcome were included in this review. Furthermore, we examined whether clinical outcomes were associated with the dosage of cilostazol (300 mg/day vs. 100–200 mg/day). Results: Data from 405 patients in 4 randomized controlled trials (RCTs) and 461 patients in 4 observational studies (OSs) were included. In RCT studies, cilostazol was associated with significant favorable outcomes at discharge or 1 month (risk ratio [RR] 1.41, 95% confidence interval [CI] 1.01–1.97, p = 0.04) or 3 or 6 months (RR 1.16, 95% CI 1.05–1.28, p = 0.002). However, in OSs, no significant difference was indicated in favorable outcomes at discharge or 1 month (RR 1.22, 95% CI 0.94–1.60, p = 0.14) nor 3 or 6 months (RR 1.29, 95% CI 0.92–1.81, p = 0.14). The analyses found that cilostazol significantly reduced the incidences of severe aVS (RCT: RR 0.64, 95% CI 0.41–1.01, p = 0.05; OS: RR 0.61, 95% CI 0.43–0.88, p = 0.007), sVS (RCT: RR 0.46, 95% CI 0.31–0.70, p = 0.0002; OS: RR 0.38, 95% CI 0.21–0.68, p = 0.001), and new cerebral infarction (RCT: RR 0.40, 95% CI 0.24–0.67, p = 0.0005; OS: RR 0.38, 95% CI 0.23–0.64, p = 0.0002). However, no significant difference in mortality (RCT: RR 0.86, 95% CI 0.23–3.21, p = 0.82; OS: RR 0.16, 95% CI 0.02–1.24, p = 0.08) was found. In 3 OSs which reported different doses of cilostazol (300 mg/day vs. 100–200 mg/day) for aSAH, the 300-mg/day cilostazol groups showed decreased delayed cerebral infarction (RR 0.27, 95% CI 0.09–0.81, p = 0.02) but no significant difference in shunt-dependent hydrocephalus (RR 0.92, 95% CI 0.33–2.60, p = 0.88) or functional outcomes (RR 1.14, 95% CI 0.74–1.75, p = 0.56) compared with the 100–200 mg/day cilostazol groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of cilostazol in treating aSAH. Furthermore, 300-mg/day cilostazol treatment appeared to be more effective than 100–200 mg/day treatment.

Clazosentan for Improvement of Time to Peak Perfusion in Patients with Angiographically Confirmed Severe Vasospasm

Clazosentan, an endothelin-1 receptor antagonist, has been shown to prevent the development of large vessel angiographic vasospasm after aneurysmal subarachnoid hemorrhage. We hypothesized that clazosentan can improve cerebral perfusion for territories affected by angiographically confirmed vasospasm. The REVERSE study (REversal of Vasospasm with clazosEntan post-aneuRysmal Subarachnoid hEmorrhage) was a prospective multicenter open-label pilot study of adult patients with aneurysmal subarachnoid hemorrhage who received intravenous clazosentan after developing moderate to severe angiographic vasospasm. Using the radiographic data from the REVERSE study and additional retrospective radiographic data from our tertiary medical center, we compared the impact of intravenous clazosentan with intraarterial vasodilator therapy (medical standard of care) on vasospasm reversal using time to peak perfusion (TTPP; the time interval between the peak opacification of contrast dye in the main artery supplying an anatomically defined territory and the parenchymal phase when the dye is diffusely present in the brain parenchyma). Both intravenous clazosentan (n = 7 vessels) and intraarterial vasodilator therapy (n = 11 vessels) resulted in a statistically significant improvement in TTPP at 24h post intervention, when compared with the TTPP just prior to intervention for territories with angiographically confirmed severe vasospasm in the proximal arteries at baseline (linear mixed-effect model, p = 0.02). The clazosentan and intraarterial vasodilator therapy groups exhibited no statistically significant interaction term [time x treatment group (medical standard of care vs. clazosentan)] in our model (p = 0.71), suggesting similar temporal course of two therapies. In our small pilot study, intravenous clazosentan administered for at least 24h had an effect comparable with that of intraarterial vasodilator therapy in reversing angiographically confirmed severe vasospasm. Our results may indicate that clazosentan, in an appropriately selected patient cohort, could offer a noninvasive approach for alleviating vasospasm.

CT angiography as a maker of severe angiographic vasospasm after aneurysmal sub arachnoid hemorrhage

Objective Severe angiographic vasospasm is a major determinant of risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, and therefore a key decisional marker for considering intensive therapies such as vasospasm angioplasty in many centers. Although CTA has been reported to be well correlated with DSA for vasospasm assessment, its indications remain unclear. We aimed to determine the accuracy of CTA compared to DSA and propose a screening algorithm of severe angiographic vasospasm using CTA. Methods A severe angiographic vasospasm was defined as a vasospasm ≥ 50% on DSA. Contemporaneous CTA and DSA imaging performed in patients at baseline and during acute vasospasm were analyzed. Vasospasm of the anterior circulation vasculature was blindly quantified up to the end of 2nd segments of both anterior and middle cerebral arteries. Two readers retrospectively analyzed 210 arterial segments in 20 consecutive patients. Skin and lens radiation doses were prospectively measured in 6 patients. Results Segment-based CTA/DSA correlation strongly depended on reader experience, imaging quality, and the absence of metallic artifact (Pearson ≤ 0.86). For the most experienced reader, patient-based certainty for excluding or confirming severe angiographic vasospasm was respectively obtained on CTA for threshold Table 1 . Conclusions Vasospasm determination on CTA remains difficult. However, with optimized imaging and experienced analysis, CTA can reliably and non-invasively rule out or confirm clinically relevant vasospasm, keeping in mind it should be performed in selected cases to prevent inutile lens radiation and contrast toxicity.

Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage – Serum D-dimer and C-reactive Protein as Early Markers

BackgroundIdentifying patients at risk for delayed cerebral ischemia after an aneurysmal subarachnoid hemorrhage remains challenging and both delayed treatment and over-treatment are reasonable concerns. ObjectiveTo evaluate the role of the serum markers C-reactive protein, white blood count, and d-dimer as prognostic factors for the occurrence of delayed cerebral ischemia. MethodsAll patients admitted within 24 hours after an aneurysmal subarachnoid hemorrhage were included over a 6-year period. The World Federation of Neurosurgery and Fisher grading scales as well as the extended Glasgow Outcome Scale were documented at discharge and after a 3-to-6-month follow-up period. C-reactive protein, d-dimer, white blood count, and procalcitonin were assessed on admission, day 1, day 4, day 9, day 14, and at discharge. Radiologically confirmed delayed cerebral ischemia before discharge was the primary endpoint. Severe angiographic vasospasm and outcome were used as secondary endpoints. ResultsDelayed cerebral ischemia occurred in 19.6% of the 138 patients included. Delayed cerebral ischemia correlated with severe vasospasm and with a worse outcome. Serum C-reactive protein levels were higher in patients with severe vasospasm during the period of vasospasm. D-dimer levels on admission correlated with Fisher grades. Delayed cerebral ischemia occurred more frequently in patients with Fisher grade IV hemorrhage, if d-dimer levels were higher on admission. The cut-off was .445 µg/ml. ConclusionOur observations support a multifactorial genesis for delayed cerebral ischemia, including vasospasm and microthrombotic and inflammatory processes. Serum d-dimer levels greater than .445 µg/ml might be a predictor for the occurrence of delayed cerebral ischemia in patients with a Fisher grade IV aneurysmal subarachnoid hemorrhage.

Effectiveness and feasibility of cilostazol in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Delayed cerebral ischemia seriously affects the prognosis of patients surviving the initial aneurysmal subarachnoid hemorrhage. Application of cilostazol was reported to ameliorate vasospasm and improve outcomes in series and clinical trials. But the effectiveness and feasibility of cilostazol on aneurysmal subarachnoid hemorrhage remained controversial. We performed a systematic review to clarify this issue. PubMed, Ovid and Cochrane library database were systematically searched up to May 2018 for eligible publications in English. Quality assessment was conducted for included studies. Meta-analysis was conducted to evaluate the overall effect on events of interest. Subgroup analyses and sensitivity analyses were used to check whether the results were robust. Publication bias was evaluated with the funnel plot. Pooled analyses found cilostazol significantly reduced incidences of severe angiographic vasospasm (p = 0.0001), symptomatic vasospasm (p < 0.00001), new cerebral infarction (p < 0.00001) and the poor outcome (p < 0.0001). Subgroup and sensitivity analyses achieved consistent results. There was no statistical difference between cilostazol and the control group in reducing mortality (p = 0.07). But sensitivity analysis changed the result after excluding one study. Under the prescribed dosage, complication was few and non-lethal. Cilostazol was effective and safe to reduce incidences of severe angiographic vasospasm, symptomatic vasospasm, new cerebral infarction and poor outcome in patients after aneurysmal subarachnoid hemorrhage. However, its effect on mortality and the interactive effect with nimodipine warranted further research.

Marked morphologic change of cerebral vessel with coexistence of severe flow compromise during endovascular treatment for ruptured aneurysm

Abstract In the vasospasm periods, the optimal timing of treatment for ruptured intracranial aneurysms remains controversial. In generally, it was recommended that treatment for a ruptured aneurysm be delayed until its disappearance, but this might be associated with aneurysmal re-rupture resulting in a poor outcome. Endovascular technique has been developed for many years, early treatment after aneurysmal subarachnoid hemorrhage (SAH) seems to be technically feasible even in the period of severe vasospasm. The present cases report our experiences of endovascular treatment for ruptured aneurysm in the presence of severe angiographic vasospasm and discuss the pertinent controversy.

Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) and Risk of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

The molecular mechanisms underlying cerebral vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) are incompletely understood. We hypothesized that circulating antiangiogenic factors, such as soluble Fms-like tyrosine kinase 1 (sFlt-1) and soluble transforming growth factor β coreceptor, soluble endoglin (sEng), are important markers of their pathophysiology. We performed a prospective study in patients with aSAH and measured cerebrospinal fluid and serum levels of sFlt-1 and sEng on postbleed day 1 and 6 and correlated levels with incidence and severity of cerebral vasospasm and DCI. Twenty-seven patients with aSAH were enrolled in the study. Severe angiographic vasospasm was present in 14.8% of patients and DCI occurred in 33.3%. Serum sFlt1 levels were increased on postbleed day 6 in patients who developed vasospasm. However, on postbleed day 1, there were no differences in patients who developed vasospasm. Increased serum sFlt-1 levels on postbleed day 1 were found to predict the development of severe angiographic vasospasm with an area under the curve of 0.818 with an optimal cutoff value of 95 pg/mL. Alterations in sFlt1 were not associated with DCI. Serum and cerebrospinal fluid sEng levels did not correlate with vasospasm or DCI. Serum levels of sFlt-1 are increased in patients with aSAH who are at risk for severe vasospasm. Further studies with larger sample sizes are needed to evaluate whether sFlt-1 levels may predict onset of severe vasospasm and DCI.

383 Fever and Leukocytosis as a Predictor of DCI After SAH

Abstract INTRODUCTION Aneurysmal subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. Delayed cerebral ischemia (DCI) is a major cause for poor outcome after SAH. Cerebral vasospasm is the primary driver of DCI, and the largest independent contributor to poor outcome after SAH. Prior studies have reported an association between fever and leukocytosis, and cerebral vasospasm. In this study, we assessed the utility of fever and/or leukocytosis to predict DCI after SAH. METHODS We performed a retrospective analysis of 187 SAH patients. Univariate and multivariate logistic regression was performed to identify potential risk factors for three different endpoints - (a) Mild, Moderate, or Severe Angiographic Vasospasm, (b) Moderate or Severe Angiographic Vasospasm, and (c) Symptomatic DCI. Multiple independent variables including age, Hunt-Hess grade, modified Fisher grade, fever (T&gt;/= 38.0 °C), WBC &gt;/= 10, WBC &gt;/= 15, fever and WBC &gt;/= 10, fever and WBC &gt;/= 15 were examined over the course of each hospital stay. RESULTS &gt;Presence of fever and/or leukocytosis were both significant predictors of symptomatic DCI. In addition, number of days with fever following aneurysm rupture was strongly associated with angiographic vasospasm, while number of days with WBC&gt;/= 15 was strongly associated with symptomatic DCI. When these variables were combined, number of days with concurrent fever and WBC&gt;/= 10 was an independent predictor of angiographic vasospasm, and number of days with concurrent fever and WBC&gt;/= 15 was an independent predictor of both angiographic vasospasm and symptomatic DCI. Time intervals of Day 0–3 and Day 3–7 after aneurysm rupture had the highest odds ratios for angiographic vasospasm. CONCLUSION Patients with aneurysmal SAH who had higher number of days with fever and/or leukocytosis after aneurysm rupture were more likely to have angiographic vasospasm and symptomatic DCI. Presence of fever and/or leukocytosis may have utility in assessing the risk of DCI following SAH.

The Barrow Neurological Institute Scale Revisited: Predictive Capabilities for Cerebral Infarction and Clinical Outcome in Patients With Aneurysmal Subarachnoid Hemorrhage

In 2012, a new computed tomography (CT) grading scale was introduced by the Barrow Neurological Institute group ("BNI scale") to predict angiographic and symptomatic vasospasm in aneurysmal subarachnoid hemorrhage. To address the question of whether BNI grading is reliable in the prediction of cerebral infarction and clinical outcome and to compare BNI scores to existing radiographic and clinical models of outcome prediction. Consecutive data of 260 patients with aneurysmal subarachnoid hemorrhage was retrospectively analyzed with respect to radiographic and clinical parameters. Patients presenting with more severe BNI grades were older ( P = .002), displayed lower Glasgow Coma Scale scores at admission ( P < .001) and were more often diagnosed with intraventricular hemorrhage ( P < .001). An increasing BNI grade was associated with higher rates of severe angiographic vasospasm ( P = .007), the occurrence of new cerebral infarction ( P < .001), and poor patient outcome ( P < .001). In contrast, analysis according to the Fisher grading system did not show a significant relationship to any outcome parameter. Multivariate analysis combining radiographic and clinical parameters showed significant results for clinical scores (Hunt and Hess and World Federation of Neurosurgical Societies) with radiographic information losing its predictive capability. The BNI scale is easily applicable and superior to the original Fisher scale regarding prediction of angiographic vasospasm, new cerebral infarction, and patient outcome. Presence of intraventricular hemorrhage and intracerebral hemorrhage are additional radiographic factors with outcome relevance that are not part of the BNI scale. Established clinical scores like World Federation of Neurosurgical Societies and Hunt and Hess grading were more relevant for outcome prediction than any radiographic information.

Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage.

Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH. Statin-naïve patients admitted <72h after WFNS ≥2 aneurysmal SAH were randomly assigned to 80mg simvastatin/day or placebo for 21days. Regional CBF was measured with quantitative (15)O PET on SAH day 7-10 before and after raising mean arterial pressure (MAP) 20-25%. Autoregulatory index (AI) was calculated as the ratio of % change in resistance (MAP/CBF) to % change in MAP. Angiography was performed within 24h of PET. Results are presented as simvastatin vs. placebo. Thirteen patients received simvastatin and 12 placebo. Clinical characteristics were similar. Moderate or severe angiographic vasospasm occurred in 42 vs. 45% and delayed cerebral ischemia in 14 vs. 55% (p=0.074). During PET studies, MAP (110±10 vs. 111±12), global CBF (41±12 vs. 43±13), and CVR (2.95±1.0 vs. 2.81±1.0) did not differ at baseline. When MAP was raised to 135±7mm Hg vs. 137±15, global CBF did not change. Global AI did not differ (107±59 vs. 0. 89±52%, p=0.68). CBF did not change in regions with low baseline flow or in regions supplied by vessels with angiographic vasospasm in either group. Six-month modified Rankin Scale scores did not differ. Our data indicate that initiation of therapy with high-dose simvastatin does not alter baseline CBF or response to induced hypertension.

Delayed infarction following aneurysmal subarachnoid hemorrhage: Can the role of severe angiographic vasospasm really be dismissed?

BackgroundThe recent literature pertaining to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage has downplayed the role of angiographic vasospasm. However, it is our hypothesis that angiographic vasospasm has a significant...

Dynamic Autoregulatory Response After Aneurysmal Subarachnoid Hemorrhage and Its Relation to Angiographic Vasospasm and Clinical Outcome.

Impaired cerebral autoregulation (CA) is increasingly recognized to contribute to sequelae after aneurysmal subarachnoid hemorrhage (SAH). The current study characterizes the course of the dynamic autoregulation index (ARI) during the first 8days after SAH and its coherence with angiographic vasospasm (VS) and clinical outcome. Fifty-one patients with SAH were prospectively included within 48h after the ictus. The ARI was determined daily for each hemisphere with the thigh cuff test. The degree of cerebral VS was evaluated based on a baseline digital subtraction angiography (DSA) after the ictus and a follow-up DSA on day 8. The clinical outcome was determined by the Modified Rankin Scale (mRS), the Glasgow Outcome Scale Extended (GOSE), and the National Institute of Health Stroke Scale (NIHSS) at discharge from the intensive care unit. Impaired CA significantly correlated with unfavorable clinical outcome scores (mRS, p=0.0021; GOSE, p=0.0027; NIHSS, p=0.0091). ARI-values of patients with a favorable clinical outcome (mRS 0-3) showed a significant improvement during the first 8days (+0.1964/day; p=0.0148) compared to a significant decrease of ARI-values in patients with an unfavorable clinical outcome (-0.2976/day; p=0.0182). The degree of CA impairment significantly correlated with the severity of VS in the middle cerebral artery (p=0.0184). Early deterioration of CA significantly correlates with unfavorable clinical outcome and severity of angiographic vasospasm. Dynamic CA measurements might represent an important tool in stratifying therapy guidelines in patients after SAH.

Institution of sustained endovascular treatment prior to clinical deterioration in patients with severe angiographic vasospasm: A retrospective observational study of clinico-radiological outcomes

Severe angiographic vasospasm (aVSP) is a risk factor for infarction following subarachnoid haemorrhage and infarction is strongly associated with poor outcome. We present the clinico-radiological results of cohort with severe aVSP who underwent a program of angiographic surveillance and sustained endovascular treatment using multiple verapamil infusions and/or transluminal balloon angioplasty (TBA). This was a dual-centre retrospective observational study. Angiographic screening for vasospasm was undertaken at days 5-7 post-ictus. Treatment was instituted principally on the basis of radiographic findings. The rate of infarction was evaluated on follow-up CT. Clinical outcome was assessed using the modified Rankin Scale (mRS). Fifty-seven WFNS grades 1-5 patients were studied. The mean number of procedures/patient was 6, range 2-13. Mean verapamil dose administered to the ICA was 14 mg and VA was 12 mg. Thirty-one patients underwent TBA (52.6%). The rate of proximal vessel infarction was 3/45 (6.7%) for patients presenting <72 hours. Rates of favourable outcome (mRS 0-2) were 16/19 (84.2%) for WFNS grades 1-2, 12/19 (63.2%) for grades 3-4 and 5/19 (26.3%) for grade 5 patients. Delayed presentation >72 hours was the only factor on multivariate analysis to significantly predict aVSP-infarction [OR19.3 (3.2-116.6) P=0.0012]. Large aVSP-infarction [OR19.0 (1.7-216.4) 0.0179] and poor WFNS grade [OR 6.6 (1.3-33.9) P = 0.0233] were significant predictors of poor outcome on multivariate analysis. This approach may result in low rates of aVSP-infarction and encouraging rates of favourable outcome when compared to literature benchmarks. Delayed presentation, however, predicts infarction and large infarct and poor initial grade significantly influence functional outcome.

The detrimental clinical impact of severe angiographic vasospasm may be diminished by maximal medical therapy and intensive endovascular treatment

ObjectiveSevere angiographic vasospasm (aVSP) is a risk factor for poor functional outcome following subarachnoid hemorrhage. We investigated the impact of angiographic surveillance and intensive endovascular treatment using transluminal balloon angioplasty...

Patient Phenotypes Associated With Outcomes After Aneurysmal Subarachnoid Hemorrhage

Predictors of outcome after aneurysmal subarachnoid hemorrhage have been determined previously through hypothesis-driven methods that often exclude putative covariates and require a priori knowledge of potential confounders. Here, we apply a data-driven approach, principal component analysis, to identify baseline patient phenotypes that may predict neurological outcomes. Principal component analysis was performed on 120 subjects enrolled in a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. Correlation matrices were created using a combination of Pearson, polyserial, and polychoric regressions among 46 variables. Scores of significant components (with eigenvalues>1) were included in multivariate logistic regression models with incidence of severe angiographic vasospasm, delayed ischemic neurological deficit, and long-term outcome as outcomes of interest. Sixteen significant principal components accounting for 74.6% of the variance were identified. A single component dominated by the patients' initial hemodynamic status, World Federation of Neurosurgical Societies score, neurological injury, and initial neutrophil/leukocyte counts was significantly associated with poor outcome. Two additional components were associated with angiographic vasospasm, of which one was also associated with delayed ischemic neurological deficit. The first was dominated by the aneurysm-securing procedure, subarachnoid clot clearance, and intracerebral hemorrhage, whereas the second had high contributions from markers of anemia and albumin levels. Principal component analysis, a data-driven approach, identified patient phenotypes that are associated with worse neurological outcomes. Such data reduction methods may provide a better approximation of unique patient phenotypes and may inform clinical care as well as patient recruitment into clinical trials. http://www.clinicaltrials.gov. Unique identifier: NCT00111085.