Association between elevated cerebrospinal fluid D-dimer levels and delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage

Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to morbidity and mortality. It is currently not possible to reliably predict patients at risk of DCI after aSAH. The aim of this study was to quantify cerebrospinal fluid (CSF) D-Dimer and plasminogen levels and to investigate any association with development of DCI. Cerebrospinal fluid (CSF) samples collected from 30 patients within 72 h post-aSAH (n = 13 DCI and n = 17 non-DCI patients) were analysed. DCI was diagnosed when angiographic vasospasm was detected in the presence of new onset neurological deficit. Enzyme-linked immunosorbent assays were used to quantify D-dimer concentrations while western blotting was used to quantify plasminogen levels. Significant differences in CSF proteins between DCI and non-DCI cohorts were verified using Mann-Whitney test. Sensitivity and specificity of these proteins for detecting DCI was examined using a ROC curve and verified with a Fischer’s exact test. CSF levels of D-dimer within 72 h post aSAH were significantly elevated in DCI patients (54.29 ng/ml, 25.35–105.88 ng/ml) compared to non-DCI patients (26.75 ng/ml, 6.9–45.08 ng/ml) [p = 0.03]. In our sample population, D-dimer levels above 41.1 ng/ml had a sensitivity of 69.2% and specificity of 75% for predicting DCI. CSF levels of plasminogen (DCI: 0.50 signal-intensity/μl, 0.20–0.73 signal-intensity/μl, non-DCI: 0.28 signal-intensity/μl, 0.22–0.54 signal-intensity/μl) did not differ between the DCI and non-DCI cohort (p > 0.05). Our study suggests that elevated D-dimer in the first 72 h after aSAH may be a potential predictive biomarker for DCI.     

Acute cervical cord syrinx after aneurysmal subarachnoid haemorrhage

We report the acute formation of a cervical cord syrinx after aneurysmal subarachnoid haemorrhage, followed by spontaneous resolution. To our knowledge, not previously described in the literature, this case provides further insights into the pathophysiology of syrinx formation, and is discussed with reference to prevailing theories.     

Update on subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) is less frequent than ischaemic stroke or intracerebral haemorrhage, but has a high public health relevance because it can affect young and middle-age adults, has considerable mortality and morbidity, it is treatable and preventable. SAH is traditionally a topic for neurosurgeons. However as endovascular interventions are becoming effective alternatives to surgical treatment, SAH should turn out to be of interest to neurologists, in particular to those devoted to stroke, emergency and neurointensive care.Despite stable incidence, the mortality of SAH has decreased in the last two decades due to better neurosurgical techniques and neurocritical care and to advances in interventional neuroradiological procedures. We review the recent advances in the clinical and diagnostic aspects of SAH and in the genetics of intracranial aneurysms. A systematic review of the treatment of SAH and grading of the available evidence is included. Presented at the “Teaching Course on Stroke”, 16th meeting of the European Neurological Society,May 26, 2006, Lausanne METHODS OF THE REVIEW: information for this review was retrieved from the author’s files and MEDLINE search of the years 2002–2006 using the key words subarachnoid haemorrhage and guidelines, review, epidemiology, genetics, treatment, clinical trials and vasospasm. Conflicts of interest. The 1^st author received travel grants from Bayer (manufacturer of nimodipine) and a research grant from the manufacturer of nicardipine.     

行血管内治疗的高龄颅内动脉瘤患者脑血管痉挛的临床分析

目的 评估70岁以上老年人动脉瘤性蛛网膜下腔出血（aSAH）患者行血管内治疗发生症状性脑血管痉挛（SCVS）的临床治疗效果。方法 44例aSHA患者分为两组:低龄组（<70岁,32例）和高龄组（≥70岁,12例）。分析两组患者的临床特征、SCVS的发生率、改良Rankin量表（mRS）评分、以及mRS评分为3~6分患者的SCVS发生率。结果 高龄组患者的SCVS发生率（58.3%）显著高于低龄组（12.5%;P<0.05）。对于mrs评分为3~6分患者,高龄组scvs发生率（58.3%）显著高于低龄组（17.4%;>P<0.05）。>结论 对于行血管内治疗的aSAH患者,≥70岁患者更易发生SCVS,从而导致更差的临床疗效和预后。     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的诊治分析

目的：探讨脑血管造影（DSA）、颅脑CT、经颅多普勒（TCD）的临床诊断价值,以及动脉瘤夹闭或血管内栓塞术、持续腰大池引流的临床治疗效果。方法61例动脉瘤性蛛网膜下腔出血患者分为观察组和对照组,对照组给予动脉瘤夹闭或血管内栓塞术,观察组在此基础上术后第2天行腰大池持续引流,观察2组患者的临床疗效,并比较术后第1、5、10天M C A血流速度、脑脊液压力、红细胞计数的变化。结果观察组总有效率达90·32％,对照组为76·67％,观察组临床疗效优于对照组,差异有统计学意义（P＜0·05）;术后第5、10天观察组大脑中动脉血流速度明显比对照组低,差异有统计学意义（P＜0·05）;术后第5、10天观察组脑脊液压力、红细胞计数均明显比对照组低,差异有统计学意义（P＜0·05）。结论 DSA、颅脑C T扫描、T CD可以明确诊断动脉瘤性蛛网膜下腔出血后脑血管痉挛,并能够评价血管痉挛的程度;采取动脉瘤夹闭或血管内栓塞术、持续腰大池引流治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛有满意效果。     

Impact of early surgery after aneurysmal subarachnoid haemorrhage

Objectives – To investigate the effect of early aneurysm surgery (<72 h) on outcome in patients with subarachnoid haemorrhage (SAH). Materials and methods – We studied two consecutive series of patients with aneurysmal SAH [postponed surgery (PS) cohort, n = 118, 1989–1992: surgery was planned on day 12 and early surgery (ES) cohort, n = 85, 1996–1998: ES was performed only in patients with Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis to assess outcome at 3 months. Results – Favourable outcome (Glasgow Outcome Scale 4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly more often in the ES cohort. The occurrence of rebleeds was similar in both cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable outcome: 6.4, 95% confidence interval (CI) 1.0–39.8] and patients with both CSS <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5, 95% CI 1.1–99.4). Conclusions – Our results support the widely adopted practice of ES in good‐grade SAH patients.     

Symptomatic cerebral vasospasm manifested 18 days after aneurysmal subarachnoid haemorrhage

Abstract

A patient who suffered rapid deterioration due to cerebral vasospasm 18 days after aneurysmal subarachnoid haemorrhage is reported. Unusually delayed onset of ischaemic neurological deficits and its preventative management is discussed. [Neurol Res 1993; 15: 209–211]     

Spasm index in subarachnoid haemorrhage: consequences of vasospasm upon cerebral blood flow and oxygen extraction

A spasm index, defined as transcranial Doppler detected flow velocity in the middle cerebral artery divided by regional cortical cerebral blood flow (CBF), was used on 24 patients with subarachnoid haemorrhage (SAH). The aim was to estimate degree and time course of vasospasm, even in cases with great day-to-day variation in CBF, and correlate to CBF and oxygen extraction. All patients showed increase in spasm indices with peak index in the second or third week. The index seemed stable in spite of day-to-day fluctuations in CBF. Severe vasospasm were associated with poor clinical condition, reduced CBF (less than 30) and high AVDO2. The same picture could be seen with minor degree of vasospasm, probably, in some cases, due to high intracranial pressure. The results suggest that the spasm index is useful in monitoring patients with subarachnoid haemorrhage, and that severe vasospasm has a negative influence on clinical condition, CBF and oxygen extraction.     

Haemodynamic and metabolic disturbances in the acute stage of subarachnoid haemorrhage demonstrated by PET

OBJECTIVE: To investigate the occurrence of early haemodynamic and metabolic changes in the acute stage of subarachnoid haemorrhage (SAH). MATERIAL AND METHODS: Eleven SAH patients were studied. Regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction ratio (OER) were measured with positron emission tomography (PET) 22-53 h after haemorrhage, utilizing 15O-labelled water bolus and the 15O-inhalation technique. Ten volumes of interest (VOIs) representing vascular territories were outlined in each patient according to a standardized procedure. The occurrence of irreversible ischaemia, penumbra, oligaemia, hyperperfusion and normal haemodynamics according to PET criteria was investigated. These pathophysiological categories were related to final tissue outcome as determined by follow-up computed tomography (CT). RESULTS: All five tissue subtypes were represented in the vascular region VOIs; oligaemia was the predominant pathophysiological pattern. When global changes were analysed, blood flow was reduced in three, oxygen metabolism was reduced in four, and OER was increased in four of seven unsedated patients, respectively. The sedated patients all had markedly reduced CBF and CMRO2 and OER in the high or supranormal range. CONCLUSION: Haemodynamic and metabolic disturbances proved to be common after SAH. These abnormalities probably reflect the primary brain injury caused by the initial haemorrhage. The impact of secondary insults such as acute hydrocephalus, brain oedema, vasospasm, seizures, hypotension and hypoxaemia are likely to be dependent on the degree of primary injury, which can be assessed by PET.     

颅内动脉瘤性蛛网膜下腔出血血管痉挛治疗的临床探讨

目的探讨颅内动脉瘤性蛛网膜下腔出血脑血管痉挛的治疗方法。方法回顾性分析颅内动脉瘤性蛛网膜下腔出血合并脑血管痉挛患者临床资料67例。结果 23例并发脑血管痉挛,6例发生一侧肢体功能障碍,3例发生脑血栓形成。经治疗后61例C-反应蛋白恢复正常,6例明显下降,4例肢体功能恢复正常,1例恢复到4级,1例死亡。结论炎症因子在脑血管痉挛中明显升高;钙离子拮抗剂尼莫地平加抗氧化剂依达拉奉中药川芎嗪联合治疗动脉瘤性蛛网膜下腔出血所致的脑血管痉挛有较好疗效。     

Importance of cerebral pan-angiography for detection of multiple aneurysms in patients with aneurysmal subarachnoid haemorrhage

In the Danish Aneurysm Study 948 patients had a ruptured intracranial aneurysm (RA) revealed by cerebral angiography. Unilateral carotid angiography (UCA) with or without vertebral angiography (VA) demonstrated the RA in 206 patients, and 16 (7.8%) unruptured aneurysms (UA) were disclosed by UCA and 1 UA by VA. In 740 patients with at least bilateral carotid angiography (BCA) 164 UA (22.2%) were disclosed by BCA and 10 by VA. I.e. the number of UA demonstrated in patients with RA is not only doubled by BCA compared to ipsilateral UCA, but tripled demonstrating that an additional UA is more likely situated on the opposite side of the RA. Pan-angiography (or at least BCA) is therefore recommended in patients with RA.     

Coping strategies in patients following subarachnoid haemorrhage

OBJECTIVES: To assess psychological coping strategies and their relationship with outcome in patients after primary subarachnoid haemorrhage (SAH). PATIENTS AND METHODS: In 51 unselected patients (24 males, 27 females; mean age 46 years) in an average 15.7+/-12.0 months after SAH usage of coping strategies were assessed by means of Estonian COPE-D test with 15 four-items scales and compared to those obtained from 51 age-, sex- and education-matched healthy persons. The data were analysed according to age, sex and education of the patients, initial severity of disease, localization of aneurysm and outcome characteristics. RESULTS: Patients after SAH reported using social support strategy less than control persons (P<0.05) with a tendency of using acceptance-oriented strategy. Task-oriented coping styles were less used (P<0.05) by patients with severe initial state, who had more marked late disability and dependence in daily living. Healthy women used social support more than men; patients and control persons 50 years or older used task-oriented strategies less than younger persons (P<0.05). CONCLUSION: The structure of coping strategies used by patients after SAH differs compared to healthy persons. The differences in using coping strategies are related to age of the patients, functional state and degree of adaptation after SAH.     

Cerebral blood flow and metabolism following subarachnoid haemorrhage: cerebral oxygen uptake and global blood flow during the acute period in patients with SAH

Forty-eight patients with subarachnoid haemorrhage were studied with repeated rCBF and CMRO2 measurements. Cortical rCBF was measured using xenon-inhalation technique. CMRO2 was calculated as AVDO2 x CBF. When first studied the 29 conscious patients showed relative hyperaemia with CBF at 50 ml and reduced CMRO2 at 2.17 ml. In the following week CBF decreased to 41. CMRO2 remained reduced and constant. The 19 unconscious patients showed initially pronounced reduction in CMRO2 to 1.26, followed by gradual increase to 1.73 in 4-5 days. Simultaneously CBF increased from 18 ml to slightly above 30 ml. In the conscious patients the early reduction in CMRO2 and the concomitant luxury perfusion may be explained by global ischaemia because of very high ICP at the time of the haemorrhage. The reduced CBF in the unconscious group could be due to increased ICP, as ventricular drainage increased CBF to levels of relative hyperaemia as demonstrated in one case. As no decrease in CMRO2 was seen during the first 2 weeks, it is suggested that ischaemia at the time of aneurysm rupture is the most important single factor in reduction of global CMRO2.     

Migraine and delayed ischaemic neurological deficit after subarachnoid haemorrhage in women: a case–control study

The aim of the present case–control study was to investigate the role of migraine as a potential risk factor for a delayed ischaemic neurological deficit (DIND) after subarachnoid haemorrhage (SAH). A telephone interview was performed in patients or their relatives to determine the prevalence of migraine. Thirty-six women aged <60 years had SAH with Hunt & Hess grade I–III and DIND (group A). This group was compared with an age-matched group of 36 female SAH patients, Hunt & Hess grade I–III without DIND (group B). The two populations were also characterized regarding hypertension, smoking, diabetes mellitus and alcohol use. A significant difference was only found for the prevalence of migraine with 47% in group A and 25% in group B ( P  < 0.05; odds ratio: 2.68, confidence interval: 0.99–7.29). Migraineurs revealed similar prevalences of risk factors independently of the presence of DINDs. This retrospective study suggests that women with migraine have a higher risk to develop a DIND than women without migraine.     

缺血修饰白蛋白评估动脉瘤性蛛网膜下腔出血患者迟发性脑缺血研究

目的探讨缺血修饰白蛋白(IMA)评估动脉瘤性蛛网膜下腔出血(a SAH)患者迟发性脑缺血(DCI)的价值及其与患者预后的关系。方法选取198例a SAH患者,根据有无DCI把患者分为DCI组和无DCI组,测定血清IMA,同时使用经颅多普勒(TCD)监测大脑中动脉的平均血流速度(VMCA),比较两组脑血管痉挛发生率和血清IMA。结果在7～10天时间段VMCA和血清IMA达到峰值,然后逐渐下降;在1～6天、7～10天、11～14天时间段,VMCA比较、血清IMA比较,差异均有统计学意义(P 0. 05)。DCI组的CVS发生率高于无DCI组,并且DCI组的血清IMA水平高于无DCI组,差异均有统计学意义(P 0. 05)。预后不良组的血清IMA[(64. 28±5. 94) U/ml]高于预后良好组[(45. 46±5. 72) U/ml],差异有统计学意义(P 0. 05)。结论血清IMA水平与脑血管痉挛及预后密切相关,它可在一定程度上反应a SAH后脑缺血情况,对血管痉挛相关的DCI评估有重要价值,并且有助于判断预后。     

血浆PTX3对动脉瘤性蛛网膜下腔出血后脑血管痉挛的预测价值

目的 分析血浆正五聚蛋白3(Pentraxin 3,PTX3)对动脉瘤性蛛网膜下腔出血后脑血管痉挛的预测价值。方法 收集本院2016年2月-2019年2月186例动脉瘤性蛛网膜下腔出血患者作为研究对象,经颅多普勒检测仪检测大脑中动脉(Middle cerebral artery,MCA)流速,MCA平均流速(Mean velocity of MCA,MCA Vm)>120 cm/s,且同侧Lindegaard≥3为血管痉挛组(92例),其余为无血管痉挛组(94例); 收集2组一般资料; 酶联免疫吸附(Enzyme linked immunosorbent assay,ELISA)法检测血浆中PTX3水平; 绘制受试者工作特性曲线(Receiver operator characteristic curve,ROC)分析血浆中PTX3对动脉瘤性蛛网膜者发生脑血管痉挛的诊断价值; 以血浆PTX3水平<4.73 ng/mL和≥4.73 ng/mL分为PTX3低表达组和PTX3高表达组,分析血浆PTX3水平与一般资料的关系; Logistic分析影响动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛的因素。结果 无血管痉挛组与血管痉挛组年龄、治疗方法、高血压病史、Fisher分级、Hunt-Hess分级存在明显差异(P<0.05); 与无血管痉挛组比较,血管痉挛组血浆PTX3水平升高(P<0.05); ROC曲线显示,血浆PTX3水平预测动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛的ROC曲线下面积为0.777,截断值为4.73 ng/mL,其敏感性为68.50%、特异性为74.50%; 血浆PTX3水平与年龄、治疗方法、Fisher分级、Hunt-Hess分级关系密切(P<0.05); Logistic分析显示,PTX3、年龄、Fisher分级、Hunt-Hess分级是影响动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛的独立危险因素。结论 动脉瘤性蛛网膜下腔出血脑血管痉挛患者血浆PTX3水平升高,PTX3对动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛具有一定诊断价值。     

Genes and outcome after aneurysmal subarachnoid haemorrhage

Objectives Initial and secondary ischaemia are important determinants of outcome after subarachnoid haemorrhage (SAH). Cerebral ischaemia is a potent stimulus for expression of genes that may influence recovery.We investigated whether functional polymorphisms in the apolipoprotein E (APOE), insulin–like growth factor-1 (IGF–1), tumor necrosis factor-A (TNF–A), interleukin-1A (IL–1A), interleukin-1B (IL–1B), and interleukin-6 (IL–6) genes are related with outcome after aneurysmal SAH. Methods Genotyping of the polymorphisms was performed in a consecutive series of 167 patients with aneurysmal SAH. The risk of a poor outcome was analysed with logistic regression with adjustment for prognostic factors for outcome after SAH, using the homozygotes for the wild type alleles as a reference. Results Patients carrying any IGF–1 non–wild type allele had a lower risk of a poor outcome (OR 0.4, 95% CI 0.2–1.0), while carriers of the TNF–A non–wild type allele had a higher risk (OR 2.3, 95% CI 1.0–5.4). We could not demonstrate an association with outcome for APOE (APOE4 OR 0.4, 95% CI 0.1–1.2; APOE 2 OR 0.7, 95% CI 0.2–2.4), IL–1A (OR 1.8, 95% CI 0.8–4.0), IL–1B (OR 0.7, 95% CI 0.3–1.5) and IL–6 (OR 0.7, 95% CI 0.3–1.8) polymorphisms. Conclusions Variation in some genes that are expressed after cerebral ischaemia may partly explain the large differences in outcome between patients with aneurysmal SAH. SAH patients homozygote for the IGF–1 wild type allele or carriers of the TNF–A non–wild type allele have a higher risk of poor outcome. Additional studies in other populations are needed to assess the generalisability of our results.     

法舒地尔联用尼莫地平预防动脉瘤性蛛网膜下腔出血后迟发性脑血管痉挛的疗效观察

目的探讨法舒地尔联用尼莫地平对预防动脉瘤性蛛网膜下腔出血后脑血管痉挛的疗效及不良反应。方法在入院后即常规给予尼莫地平静脉持续泵入的同时,将50例动脉瘤性蛛网膜下腔出血患者在作动脉瘤栓塞治疗后,均给予腰大池引流及"3H"疗法,并随机分成2组,治疗组加用盐酸法舒地尔30mg静滴,3次/d,连用14d,观察2组血管痉挛的发生情况及不良反应。结果治疗组症状性脑血管痉挛1例,无症状性脑血管痉挛3例,对照组症状性脑血管痉挛3例,无症状性脑血管痉挛10例,2组间差异有统计学意义(P<0.05)。不良反应方面2组比较差异无统计学意义。结论法舒地尔联用尼莫地平在预防动脉瘤性蛛网膜下腔出血所致血管痉挛的疗效优于单用尼莫地平,安全性亦较高。     

Arachidonate metabolites and vasospasm after subarachnoid haemorrhage

A wide literature exists about the pathogenesis of cerebral arterial spasm following subarachnoid haemorrhage: several compounds have been identified in human cerebrospinal fluid as possible vasoactive agents involved in the biochemical mechanism of vasospasm onset. Many experimental evidences exist for a major involvement of arachidonate metabolites. The present work represents a review of experimental data supporting the hypothesis of cerebral arterial spasm as a result of an imbalanced vascular regulatory mechanism involving arachidonate metabolites. The authors have also monitored, in 25 cases of aneurysmal subarachnoid haemorrhage, lumbar and cisternal CSF levels of prostacyclin and PGD₂, as representative of vasodilating and, respectively, vasoconstrictor compounds. In all cases CSF arachidonate metabolite levels after SAH were significantly higher than in control cases. Ten patients presented with symptomatic vasospasm: lumbar CSF PGD₂ levels show fluctuations with superimposed peaks related to the neurological deterioration due to vasospasm, while lumbar CSF prostacyclin concentration-trend suggest a decreasing synthesis. In 15 patients presenting without vasospasm, lumbar CSF concentration of arachidonate metabolites are in a 'steady-state'. These data confirm the existence of an imbalanced biochemical situation promoting vasospasrn, markedly in cisterns near to the ruptured aneurysmal wall. The evaluation of cisternal CSF levels of arachidonate metabolites supports the hypothesis of the clotting phenomenon around the ruptured aneurysm as an important predictive pattern of vasospasm, as shown in CT findings.     

Cognitive functioning after subarachnoid haemorrhage of unknown origin

Twenty patients, who had sustained a proven subarachnoid haemorrhage (SAH) and in whom cerebral panangiography had failed to reveal any source of the bleeding (SAH-NUD), were subjected to a neuropsychological examination involving memory functions, spatial perceptual organization, visuoconstructive abilities, reasoning, perceptual speed and accuracy, and concept formation. Cognitive functioning in SAH-NUD patients was compared with normal reference values and also related to the cognitive performance of neurologically intact patients having sustained an aneurysmal bleeding (SAH-AN). SAH-NUD patients showed significant reduction of verbal learning and retention, and of abilities involving abstract attitude and concept formation, i.e., functions related to frontotemporal structures. In all other respects the performance of these patients approached normality. Unexpectedly, there were no significant differences in mean test scores separating SAH-NUD from aneurysmal SAH patients. Collapsing the patient groups produced an increased number of significant deviations from normality, which was interpreted as the effect of the contribution of a greater number of relatively more impaired SAH-AN patients. This was supported by the finding that the ratio of impaired individuals to total number of subjects differed in the groups; the proportion of individuals showing cognitive sequelae was larger among SAH-AN patients throughout all comparisons but one. Although SAH of unknown aetiology represents much less of a catastrophe as compared with haemorrhage of aneurysmal origin, it does not preclude cognitive disturbances. Thus, the presence of blood per se anywhere in the subarachnoid spaces appears to affect higher brain function(s).