Intraarterial Nimodipine Infusion to Treat Symptomatic Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Objective

Cerebral vasospasm leading to cerebral ischemic infarction is a major cause of morbidity and mortality in the patients who suffer with aneurysmal subarachnoid hemorrhage. Despite adequate treatment, some patients deteriorate and they develop symptomatic vasospasm. The objective of the present study was to investigate the efficacy and clinical outcome of intraarterial nimodipine infusion on symptomatic vasospasm that is refractory to hemodynamic therapy.

Methods

We retrospectively reviewed the procedure reports, the clinical charts and the transcranial doppler, computed tomography and digital subtraction angiography results for the patients who underwent endovascular treatment for symptomatic cerebral vasospasm due to aneurysmal SAH. During the 36 months between Jan. 2005 and Dec. 2007, 19 patients were identified who had undergone a total of 53 procedures. We assessed the difference in the arterial vessel diameter, the blood flow velocity and the clinical outcome before and after these procedures.

Results

Vascular dilatation was observed in 42 of 53 procedures. The velocities of the affected vessels before and after procedures were available in 33 of 53 procedures. Twenty-nine procedures exhibited a mean decrease of 84.1 cm/s. We observed clinical improvement and an improved level of consciousness with an improved GCS score after 23 procedures.

Conclusion

Based on our results, the use of intraarterial nimodipine is effective and safe in selected cases of vasospasm following aneurysmal SAH. Prospective, randomized studies are needed to confirm these results.     

Timing of Computed Tomography and Prediction of Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Background  The initial noncontrast computed tomography (CT) study of the head after an aneurysmal subarachnoid hemorrhage (SAH) is used to predict the risk of developing vasospasm. Changes in the extent of subarachnoid blood seen on CT images occur as a function of time after SAH, but there is no consensus on the time interval during which this study needs to be completed. Methods  Clinical and radiological information on adult SAH patients were reviewed. Patients were grouped based on the time elapsed from ictus to the initial head CT study. The amount of subarachnoid blood on CT was graded using the Hijdra sum score (HSS) and the modified Fisher scale (MFS). The relationship between the initial CT grading score and the risk of angiographic vasospasm was assessed for each group. Results  A total of 224 consecutive patients were identified (145 females, 65%). Initial CT was performed within 24 h of the event in 163 (Group 1, 73%) and after 24 h in 61 patients (Group 2, 27%). A total of 54 patients (24%) developed angiographic vasospasm. A statistically significant association between the extent of subarachnoid blood and subsequent development of vasospasm was observed only if the initial CT imaging study was performed within 24 h of aneurysmal rupture (P = 0.0001 and 0.02 for HSS and MFS, respectively). Conclusions  We propose that only CT scans obtained within 24 h of a subarachnoid bleeding event should be used to estimate the risk of vasospasm.     

Intraventricular Nicardipine for Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage

Introduction  Delayed ischemic deficit from vasospasm is a leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Although several treatment modalities have been used to reverse the deleterious effects of vasospasm, alternative therapies are needed, as conventional therapies are often ineffective or contraindicated. Intrathecal nicardipine has been suggested for the prevention of vasospasm. We report our clinical experience with intraventricular nicardipine for refractory vasospasm in eight patients in whom conventional therapies were ineffective, contraindicated, or technically not feasible. Method  Retrospective case series performed at a tertiary care university hospital. Results  Eight patients (median Hunt-Hess grade = 2, median Fisher score = 4) with refractory vasospasm received intraventricular nicardipine (4 mg every 12 h) for a total of 5–17 days. One patient died in the intensive care unit. Seven patients had moderate to good outcomes with 6 being discharged to home (median Rankin Score = 2). Intraventricular nicardipine was well tolerated with minimal side effects. Conclusion  Our preliminary observations suggest that intraventricular nicardipine could be considered as a safe and effective treatment modality to treat vasospasm refractory to conventional management. A randomized, controlled trial to verify the efficacy and safety of intrathecal nicardipine in the prevention and treatment of cerebral vasospasm is warranted.     

Significance of C-Reactive Protein and Transcranial Doppler in Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Objective

Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. C-reactive protein (CRP) constitutes a highly sensitive inflammatory marker. Elevation of serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between CRP levels in the serum and transcranial Doppler (TCD) and the development of vasospasm in patients with aSAH.

Methods

A total of 61 adult patients in whom aSAH was diagnosed were included in the study from November 2008 to May 2011. The patients'' demographics, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum CRP measurements were obtained on days 1, 3, 5, 7, 9, 11 and 13 and TCD was measured on days 3, 5, 7, 9, 11 and 13. All patients underwent either surgical or endovascular treatment within 24 hours of their hemorrhagic attacks.

Results

Serum CRP levels peaked on the 3rd postoperative day. There were significant differences between the vasospasm group and the non-vasospasm group on the 1st, 3rd and 5th day. There were significant differences between the vasospasm group and the non-vasospasm group on the 3rd day in the mean middle cerebral artery velocities on TCD.

Conclusion

Patients with high levels of CRP on the 1st postoperative day and high velocity of mean TCD on the 3rd postoperative day may require closer observation to monitor for the development of vasospasm.     

Reduced Ipsilateral Hemispheric Cerebral Blood Flow at Admission is Predictive of Vasospasm with Infarction after Aneurysmal Subarachnoid Hemorrhage

Background and Purpose  Cerebral vasospasm (CV) with infarction causes a significant degree of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine if reduced cerebral blood flow (CBF) on Xenon CT within 48 h of the ictus was predictive of developing CV with infarction. Methods  This is a prospective study from 1999 to 2006 of 97 patients with aSAH who underwent Xenon CT within 48 h of their bleed. Demographic, clinical, radiographic, and angiographic parameters were investigated as potential risk factors for the development of CV with infarction. A binary logistic regression analysis was performed to determine the independent predictors of this endpoint. Results  A total of 97 patients with a mean age of 54 ± 12 years were studied. A total of 78 (80.4%) patients presented with a Fisher grade of 3 and 51 (52.6%) patients with a Hunt Hess score ≥3. CV with infarction was found in 33 (34%) patients. In univariate modeling, younger patients with a Fisher scale of 3 or a reduced ipsilateral mean hemispheric CBF had an association with developing CV with infarction. In binary logistic regression modeling, patients with lower initial hemispheric CBF’s were at a significant risk of CV with infarction in the ipsilateral hemisphere. Conclusions  Lower initial CBF at presentation is a risk factor for developing CV with infarction. These findings may help in early prediction of this entity and may have therapeutic implications in the future.     

Safety and Efficacy of Transluminal Balloon Angioplasty Using a Compliant Balloon for Severe Cerebral Vasospasm after an Aneurysmal Subarachnoid Hemorrhage

Objective

Vasospasm of cerebral vessels remains a major source of morbidity and mortality after an aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to evaluate the safety and efficacy of transluminal balloon angioplasty (TBA) for SAH-induced vasospasm.

Methods

Eleven patients with an angiographically confirmed significant vasospasm (>50% vessel narrowing and clinical deterioration) were studied. A total of 54 vessel segments with significant vasospasm were treated by TBA. Digital subtraction angiography was used to confirm the presence of vasospasm, and TBA was performed to dilate vasospastic arteries. Medical and angiographic reports were reviewed to determine technical efficacy and for procedural complications.

Results

TBA using Hyper-Glide or Hyper-Form balloons (MicroTherapeutics, Irvine, CA) was successfully accomplished in 88.9% vasospastic segments (48 of 54), namely, in the distal internal carotid artery (100%, n=7), the middle cerebral artery (100%), including the M1 (n=10), M2 (n=10), and M3 segments (n=4), in the vertebral artery (100%, n=2), basilar artery (100%, n=1), and in the anterior cerebral artery (ACA), including the A1 (66%), A2 (66%), and A3 segments (100%). Vessel diameters significantly increased after TBA. There were no cases of vessel rupture or thromboembolic complications. GCS at one day after TBA showed an improvement in all patients except one.

Conclusion

This study suggests that TBA using Hyper-Glide or Hyper-Form balloons is a safe and effective treatment for subarachnoid hemorrhage-induced cerebral vasospasm.     

Relationship Between Hemoglobin Concentrations and Outcomes Across Subgroups of Patients with Aneurysmal Subarachnoid Hemorrhage

Objective  Anemia predicts poor outcome following aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that this association would be stronger among patients with more severe SAH, since these patients are likely to be more vulnerable to secondary brain injury in the form of reduced cerebral oxygen delivery. Methods  Daily nadir hemoglobin (Hb) concentrations over 2 weeks following SAH were retrieved in 245 consecutive patients, and compared between those with a favorable versus unfavorable outcome. The analysis was repeated with patients dichotomized as follows: WFNS score 4–5 vs. 1–3; modified Fisher score (MFS) 4 vs. 0–3; and vasospasm present vs. absent. Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data with repeated measures. Results  Patients with an unfavorable outcome consistently had lower Hb concentrations, especially between days 6–11 following SAH (P ranging from <0.001 to 0.009), as well as a greater fall in Hb over time (β = −0.07, P < 0.001). This was true regardless of WFNS score, MFS, or the presence or absence of vasospasm. However, the effect was somewhat more pronounced among patients with higher WFNS and modified Fisher scores. Conclusion  Lower Hb levels are associated with worse outcomes regardless of SAH severity or the development of vasospasm. This finding may imply that a lower Hb concentration is largely a marker for a greater degree of systemic illness, rather than necessarily causing direct harm. However, the association is somewhat stronger among patients with more severe SAH. Thus, if there is a benefit for maintaining higher Hb levels with transfusions or erythropoietin, it may be more pronounced among these patients. Supported in part by the Louise Nerancy endowment of The University of Virginia.     

动脉瘤性SAH迟发性脑血管痉挛的多元因素分析

目的 探讨动脉瘤性蛛网膜下腔出血（SAH）继发脑血管痉挛的相关因素。方法 回顾性分析本院收治的54例动脉瘤性SAH病人的临床资料，判定脑血管痉挛程度，统计分析其相关因素。结果Fisher分级Ⅲ-Ⅳ级患者脑血管痉挛发生率（7014％，19／27）明显高于Fisher分级Ⅰ-Ⅱ级者（4414％，12／27）（P〈0．01）；Hunt—Hess分级Ⅲ-Ⅴ级患者脑血管痉挛发生率（75．0％，21／28）明显高于Hunt—Hess分级Ⅰ-Ⅱ级者（38．5％，10／26）（P〈0．05）；3d后手术患者的脑血管痉挛发生率（70．0％，21／30）明显高于3d内手术患者（41．7％，10／24）（P〈0．05）。结论SAH的Fisher分级〉Ⅱ级和Hunt—Hess分级〉Ⅱ级是颅内动脉瘤继发脑血管痉挛的危险因素。早期手术能降低脑血管痉挛的发生率。     

Intravenous Magnesium Infusion for the Prevention of Symptomatic Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Objective

The study examined the difference in the incidence of symptomatic cerebral vasospasm with magnesium supplementation in aneurysmal subarachnoid hemorrhage (SAH) in a Korean population.

Methods

This retrospective analysis was performed in 157 patients diagnosed with aneurysmal SAH from January 2007 to December 2011 at a single center. Seventy patients (44.6%) received a combination treatment of nimodipine with magnesium and 87 patients (55.4%) received only nimodipine. A matched case-control study using propensity scores was conducted and 41 subjects were selected from each group. A dosage of 64 mmol/day of magnesium was administrated.

Results

The infusion of magnesium did not reduce the incidence of symptomatic cerebral vasospasm (n=7, 17.1%, p=0.29) compared with simple nimodipine injection (n=11, 26.8%). The ratios of good clinical outcome (modified Rankin scale 0-2) at 6 months were similar, being 78% in the combination treatment group and 80.5% in the nimodipine only group (p=0.79). The proportions of delayed cerebral infarction was not significantly lower in patients with combination treatment (n=2, 4.9% vs. n=3, 7.3%; p=0.64). There was no difference in the serum magnesium concentrations between the patients with symptomatic vasospasm and without vasospasm who had magnesium supplementation. No major complications associated with intravenous magnesium infusion were observed.

Conclusion

Magnesium supplementation (64 mmol/day) may not be beneficial for the reduction of the incidence of symptomatic cerebral vasospasm in patients with aneurysmal SAH.     

Monitoring with the Somanetics INVOS 5100C After Aneurysmal Subarachnoid Hemorrhage

Introduction  Vasospasm is a major cause of morbidity after subarachnoid hemorrhage (SAH), and current screening techniques (angiography, transcranial Doppler [TCD], and clinical examination) have serious limitations. Brain oximetry is a promising noninvasive tool to detect reduced brain oxygenation from vasospasm. Methods  Consecutive SAH patients at high risk for vasospasm were monitored with the INVOS (Somanetics, IL, USA) 5100C cerebral oximeter. We prospectively collected oximeter readings (rO2) with concurrent values for vital signs, intracerebral pressure (ICP), arterial blood gas measurement, and hemoglobin (HGB). Data were prospectively collected every 12 h and at clinical events (angiography, transfusion, etc.). We prospectively recorded clinical history, clinical events, radiology results, and outcomes. Results  Six patients were measured 123 times. rO2 values were correlated with the contralateral side, HGB, blood pressure, and PaO2, but not with ICP or perfusion pressure. There were no measured effects of angiography or transfusion. Patterns relating rO2 readings to clinical, angiographic, or TCD evidence of vasospasm were unclear, and there were no associations with the outcome (cerebral infarction, NIH Stroke Scale, or modified Rankin Scale). Conclusion  INVOS rO2 readings are associated with other factors that relate to cerebral oxygen delivery but seem to be of limited use as a screening tool for vasospasm or cerebral infarction after SAH.     

The Burden of the Systemic Inflammatory Response Predicts Vasospasm and Outcome after Subarachnoid Hemorrhage

Introduction  Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce the systemic inflammatory response syndrome (SIRS). This may promote both extra-cerebral organ dysfunction and delayed cerebral ischemia, contributing to worse outcome. We ascertained the frequency and predictors of SIRS after spontaneous SAH, and determined whether degree of early systemic inflammation predicted the occurrence of vasospasm and clinical outcome. Methods  Retrospective analysis of prospectively collected data on 276 consecutive patients admitted to a neurosciences intensive care unit with acute, non-traumatic SAH between 2002 and 2005. A daily SIRS score was derived by summing the number of variables meeting standard criteria (HR >90, RR >20, Temperature >38°C, or <36°C, WBC count <4,000 or >12,000). SIRS was considered present if two or more criteria were met, while SIRS burden over the first four days was calculated by averaging daily scores. Regression modeling was used to determine the relationship among SIRS burden (after controlling for confounders including infection, surgery, and corticosteroid use), symptomatic vasospasm, and outcome, determined by hospital disposition. Results  SIRS was present in over half the patients on admission and developed in 85% within the first four days. Factors associated with SIRS included poor clinical grade, thick cisternal blood, larger aneurysm size, higher admission blood pressure, and surgery for aneurysm clipping. Higher SIRS burden was independently associated with death or discharge to nursing home (OR 2.20/point, 95% CI 1.27–3.81). All of those developing clinical vasospasm had evidence of SIRS, with greater SIRS burden predicting increased risk for delayed ischemic neurological deficits (OR 1.77/point, 95% CI 1.12–2.80). Conclusions  Systemic inflammatory activation is common after SAH even in the absence of infection; it is more frequent in those with more severe hemorrhage and in those who undergo surgical clipping. Higher burden of SIRS in the initial four days independently predicts symptomatic vasospasm and is associated with worse outcome. Financial support: Supported by NIH-N535906 (MND).     

法舒地尔预防蛛网膜下腔出血后脑血管痉挛的系统性研究

目的   系统评价法舒地尔对蛛网膜下腔出血患者脑血管痉挛预防疗效价值。 方法  检索医学文献数据库,筛选法舒地尔对蛛网膜下腔出血患者脑血管痉挛预防疗效对照试验,统计模型为随机效应模型,应用Stata?12.0软件进行Meta分析。 结果  共7项临床研究符合纳入标准,包含709例患者。与对照组比较,法舒地尔治疗组脑血管痉挛发生率：合并相对危险度（risk ratio,RR）为0.54,95%可信区间为（0.38,0.77）,P＜0.05。分别进行以下因素分层分析：改良Jadad评分≥4的研究结果、不同国别（中国与日本）的研究结果、尼莫地平作为对照组,以上分层分析结果表明法舒地尔治疗组脑血管痉挛发生率并未显著低于对照人群。 结论  对于蛛网膜下腔出血患者,法舒地尔能够降低脑血管痉挛发生率。     

蛛网膜下腔出血患者继发症状性脑血管痉挛的相关危险因素分析

目的 研究探讨动脉瘤性蛛网膜下腔出血（subarachnoid hemorrhage,SAH）继发症状性脑血管痉挛 （symptomatic cerebral vasospasm,SCVS）的相关危险因素,为SCVS的防治提供参考。 方法 回顾性分析96例SAH患者临床资料,对性别、年龄、高血压史、糖尿病史、Fisher分级等影响因 素进行统计学分析。 结果 96例患者中发生SCVS的患者共39例,单因素分析结果显示SCVS组与非SCVS组在年龄、高血 压、吸烟、脑室内积血、Hunt-Hess分级、Fisher分级、数字减影血管造影（digital subtraction angiography, DSA）显示血管痉挛程度、尼莫地平使用等方面差异有显著性;多因素Logistic回归分析结果显示：低 龄、高血压史、Fisher分级是发生SCVS的危险因素,其比值比（odds ratio,OR）分别为0.567、1.982和 2.713;而尼莫地平的使用是SCVS发生的保护因素,OR为0.799。 结论 SAH后SCVS是多种因素共同作用的结果,其中低年龄、高血压史、Fisher分级是SCVS的独立危 险因素,尼莫地平使用为保护因素。     

蛛网膜下腔出血后迟发性脑血管痉挛的发病机制和治疗进展

脑血管痉挛（cerebral vasospasm,CVS）是蛛网膜下腔出血（subarochnoid hemorrhage,SAH）最 严重的并发症,尤其是迟发性脑血管痉挛（delayed cerebral vasospasm,DCV）,一旦发生可能会出现 脑缺血甚至死亡等严重并发症。目前其发病机制尚不明确,多种因素如红细胞分解产物、一氧化氮 （nitric oxide,NO）、内皮素、自由基和脂质过氧化物等均是导致DCV的重要因素,而对于治疗DCV的方 法也在持续探索中,SAH后DCV仍是目前面临的一大难题。本文主要对SAH后CVS的发病机制及治疗进 展进行综述。     

Inpatient Hyperglycemia Following Aneurysmal Subarachnoid Hemorrhage: Relation to Cerebral Metabolism and Outcome

Introduction  Despite its clear association with impaired prognosis, it remains controversial whether hyperglycemia after aneurysmal subarachnoid hemorrhage (SAH) actively contributes to neuronal damage. This study aimed to identify a threshold for blood glucose predicting unfavorable outcome, and to evaluate differences in cerebral metabolism in normo and hyperglycemic SAH patients. Methods  Prospectively, blood glucose and cerebral metabolism, measured by cerebral microdialysis, were evaluated in 178 patients (WFNS grade I–V; age 51.6 ± 12.4 years) during days 1–7 after SAH. Patients were classified into groups with mean blood glucose levels ≤/> 6.1 mmol/l (110 mg/dl) and 7.8 mmol/l (140 mg/dl). Glasgow Outcome Score was assessed after 12 months. Results  Higher inpatient blood glucose was associated with impaired prognosis, with a threshold of 7.5 mmol/l (135 mg/dl) distinguishing best between favorable and unfavorable outcome. Inpatient glucose levels >6.1 mmol/l (110 mg/dl) were associated with higher cerebral lactate and lactate/pyruvate ratio (P < 0.05). Cerebral glucose was elevated only at blood levels >7.8 mmol/l (140 mg/dl). Inpatient glucose levels above 7.8 mmol/l (140 mg/dl) were independent predictors of unfavorable outcome and mortality. Conclusion  Blood glucose levels >7.8 mmol/l (140 mg/dl), but not levels >6.1 mmol/l (110 mg/dl), independently predicted unfavorable outcome. While blood glucose levels >6.1 mmol/l (110 mg/dl) were already associated with slight metabolic derangements, cerebral glucose increased only at blood levels >7.8 mmol/l (140 mg/dl). Considering the risks associated with tight glycemic control, a moderate regimen accepting blood glucose levels up to 7.8 mmol/l (140 mg/dl) might be more reasonable after SAH.     

动脉瘤性蛛网膜下腔出血后慢性脑积水

目的探讨动脉瘤性蛛网膜下腔出血后(aSAH)慢性脑积水的发生率及其易患因素。方法回顾性研究2003年1月至2005年9月我科aSAH病例221例,采用单因素及多因素统计方法分析与慢性脑积水发生的相关影响因素。结果慢性脑积水的发生率为12.7%(28/221)。经单因素分析显示,患者年龄、Hunt-Hess级别、Fisher级别、前交通动脉瘤、aSAH次数以及脑室内出血具有统计学意义;多因素logistic回归分析显示,Fisher级别、脑室内出血、aSAH次数、前交通动脉瘤具有统计学意义。结论慢性脑积水为aSAH后一较常见并发症,影响其发生的高危因素包括Fisher级别、脑室内出血、aSAH次数、前交通动脉瘤。对具上述危险因素的aSAH患者应注意跟踪随访,及时诊治。     

Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis

Objectives

Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH).