Normovolaemic induced hypertension therapy for cerebral vasospasm after subarachnoid haemorrhage

Summary We showed that normovolaemic induced hypertension therapy was effective in reducing ischaemic symptoms attributed to cerebral vasospasm in 41 patients after subarachnoid haemorrhage. By inducing hypertension to 25% to 50% above normal systolic arterial blood pressure, we observed that in 17 of 24 cases (71%) neurological deficits improved. In four cases of haemorrhagic infarction, the blood pressure rose to over 50% of systolic arterial pressure, and a low density area was confirmed on computerized tomography (CT) scan prior to vasospasm. Induced hypertension was therefore not considered when a low density area was revealed on CT scan.Restriction of fluid input is usually a factor in producing hypovolaemia after a neurosurgical operation. Intravascular volume expansion has been reported effective in reversing ischaemic deficits. However, according to Poiseuille's equation, increasing blood volume to a state of hypervolaemia can not enhance flow. The cerebral blood flow (CBF) was raised by increasing perfusion pressure, reducing viscosity, or increasing blood vessel diameter. Intravascular volume expansion elevates not only systemic arterial pressure, but also pulmonary artery wedge pressure over 18 mmHg and cardiac index over 2.2. Since pulmonary oedema and congestive heart failure may develop, one should monitor haemodynamic parameters with the Swan-Ganz catheter as a preventive measure.We emphasize that normovolaemic induced hypertension, maintaining haemodynamics subset 1 of the comparable haemodynamic subsets, is effective in raising perfusion pressure of CBF.     

CO2 reactivity of cerebral vasospasm after aneurysmal subarachnoid haemorrhage

CO2 reactivity of the brain vessels was investigated in 33 patients (Grade I-III after Hunt and Hess) with cerebral vasospasm after an aneurysmal subarachnoid haemorrhage (SAH) and after early operation within 72 hours. In all cases, transcranial Doppler sonography was used to measure flow velocities in the middle cerebral artery (MCA) and internal carotid artery (ICA) and vasomotor reactivity to CO2 changes. Vasospastic conditions lead to higher flow velocities through the narrow segment, lower peripheral stream resistance due to the post-stenotic pressure drop and lower vasodilating capacities of arterioles under hypercapnia. In severe vasospastic conditions, the peripheral stream bed is already maximally dilated and the hypercapnic response is weak. On the other hand, the peripheral vascular bed reacts normally to hypocapnia in all vasospastic situations. Our results point out two dangerous conditions of vasospastic disease: 1) exhaustion of peripheral vasodilating capacities, and 2) hyperventilatory therapy. Both of these situations can result in a reduction of CBF to brain tissue, mainly for two reasons: 1) In the former, a further increase in vasospasm cannot be compensated for anymore when the peripheral arterioles are maximally dilated, and 2) in the latter, hypocapnia produces a strong peripheral vasoconstrictor response with further reduction of CBF.     

Effect of hyperdynamic therapy on cerebral ischaemia caused by vasospasm associated with subarachnoid haemorrhage

Summary Ten patients who developed neurological deficits associated with angiographically proven cerebral vasospasm caused by ruptured aneurysm were treated with hyperdynamic therapy induced by administration of a large amount of human serum albumin. No vaso-active drugs were administered. Cardiopulmonary function and intracranial pressure were monitored during the treatment. Marked improvement of neurological function was observed in all cases. Nine patients recovered completely without any neurological residual following treatment. The degree of the improvement observed during treatment closely correlated with the decrease in total peripheral resistance. Infusion of albumin did not cause elevation of intracranial pressure. It was concluded that the hyperdynamic therapy induced by administration of albumin has a dramatic effect on the ischaemic cerebral insult caused by vasospasm. It is postulated that the main effect of this treatment is produced by cerebrovascular dilatation.     

Magnesium protection against in vitro cerebral vasospasm after subarachnoid haemorrhage.

Mg2+ has recently been proposed for the treatment of cerebral vasospasm and is known to dilate vessels. In this study, we examine the effects of Mg2+ on in vitro vasospasm using CSF from vasospastic subarachnoid haemorrhage patients with vasospasm (CSFv). Oxygen consumption and isometric force measurements in the porcine carotid artery were used to assess the contractile and metabolic status of the vessels' responses to CSFv and the effect of Mg2+. Mg2+ caused a dose dependant decrease in tension following contraction by CSFv. Mg2+ (12 mM) caused a normalization of relaxation rate in tissue exposed to CSFv, caused a significant decrease in basal oxygen consumption, as well as significantly decreasing the rate of oxygen consumption of the porcine carotid artery when stimulated by CSF (0.70 +/- 0.12 versus. 0.46 +/- 0.1 micromol O2 min(-1) g(-1)). Acute Mg2+ addition demonstrated the most effective protection using an assay based on CSFv contraction. These results suggest that Mg2+ can protect vascular smooth muscle exposed to CSFv by benefiting contractile behaviour and metabolism of the arteries.     

Anti-phospholipid antibodies and cerebral vasospasm following subarachnoid haemorrhage

Summary Delayed ischaemic deficits due to cerebral vasospasm contribute to the high morbidity and mortality rates associated with subarachnoid haemorrhage. We evaluated the usefulness of measuring anti-phospholipid antibodies (aPLs) for prediction of the occurrence of symptomatic vasospasm and the outcome after subarachnoid haemorrhage. 32 consecutive patients with subarachnoid haemorrhage due to ruptured cerebral aneurysms were studied. They were admitted and operated on within 72 hours after the onset of subarachnoid haemorrhage. aPLs such as lupus anticoagulants, anti-cardiolipin IgG and anti-cardiolipin IgM were measured repeatedly after admission. Furthermore, platelet count, platelet aggregability and plasma platelet factor 4 were also measured. Eleven among the 32 patients (34.4%) showed positive in the examination for aPLs. Although aPLs could not predict symptomatic vasospasm, once symptomatic vasospasm occurred, patients with aPLs frequently demonstrated cerebral infarction and there-fore their outcome was worse. aPLs were associated with a severe initial clinical grade and SAH grade on CT scan. Therefore it may explain the association of aPLs with worse outcome. aPLs were detected between 1 and 7 days. Four of 6 patients (67%) with aPLs became negative between 7 and 13 days after subarachnoid haemorrhage. The mechanism of transient aPLs is unclear but it is more likely to occur in the severer grade patients. The reduction in platelet count, the increased platelet aggregability, and the increased plasma platelet factor 4 concentration were also observed in aPLs-positive patients with symptomatic vasospasm.     

Early diagnostic for vasospasm after aneurysmal subarachnoid haemorrhage

Vasospasm is the leading cause of sequelae or deaths after aneurysmal subarachnoid haemorrhage. Vasospasm occurs 2-10 days after haemorrhage and that justifies close monitoring during this period. Because clinical signs appear often to late to reverse ischaemia, paraclinic tools have been developed. Arteriography is the historical gold standard for diagnosis but no clear validated rules exist to measure vessel sections. Diagnosis of vasospasm is, thus, relatively subjective and only reflects one moment of arteries status. Transcranial doppler is a non-invasive and easily repeatable method but sensibility and specificity for vasospasm diagnosis are low compared to arteriography. However, day-to-day changes of arterial blood cells velocities can help to determine vasospasm risk and/or indicate time for arteriography. CT-scanner, PET-scan or IRM can help to evaluate ratio between perfusion and metabolism. Nevertheless, as arteriography, it is only a one-time measurement without control of treatment effects. Waiting for improvement of diagnosis techniques, arteriography stays the gold standard. To choose the right moment for invasive methods, intensivists need to use clinical and transcranial doppler data and start treatment as early as possible to be efficacious.     

A new animal model for monitoring the early cerebral vasospasm after subarachnoid haemorrhage

AIM: Spasm of cerebral arteries is a complication associated with subarachnoid haemorrhage. The aim of the present work is to find an experimental model of reliable, simple and in vivo monitoring of 'early' basilar artery spasm after subarachnoid haemorrhage (SAH). Early spasm occurs within minutes of the SAH, its duration is approximately 1 hour. The need of different morphological and haemodynamic methods to evaluate experimental early spasm is reported. METHODS: To overcome intracranial surgical manipulations and biological of contrast and fixation media we designed a model that allows in vivo functional monitoring of basilar blood flow far away from the spasm without direct surgical and chemical interferences. Seventeen adult Burgundy rabbits were studied. RESULTS: Under homeostatic monitoring 'on-line' carotid blood flow (carotid BF) .changes produced by SAH in cisterna magna of 12 (plus 5 sham treated) animals were studied from the common carotid artery after external carotid artery occlusion before, during SAH up to the end of the experiments. All the animals underwent digital subtraction cerebral panangiography (CPA) after SAH obtaining a significant increase of carotid BF only when basilar vasospasm was shown by CPA. CONCLUSIONS: Carotid BF increase during basilar vasospasm was defined 'functional. monitoring' of early spasm.     

Does thrombin prevent cerebral vasospasm following aneurysmal subarachnoid haemorrhage?

Fibrinopeptide A (FPA) levels which have been shown to be a quantitative index of thrombin generation, were measured in blood and cerebrospinal fluid (CSF) samples from patients following subarachnoid haemorrhage (SAH) and from a control population. The levels found in samples obtained in patients following SAH are compared with those found in controls and also correlated with clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons' grading system, and with the amount of subarachnoid blood seen on CT, the occurrence of ischaemic deterioration, the occurrence of low-density change on CT, the presence of vasospasm on angiography, clinical outcome as assessed by the Glasgow Outcome Score 3 months following the ictus, and the incidence of ischaemia as a cause of death or disability as assessed 3 months following the ictus. The levels of FPA found in blood and CSF from patients following SAH were significantly raised when compared with those found in controls. There was significant correlation between blood FPA levels and the amount of subarachnoid blood seen on initial CT. CSF FPA levels had a statistically significant correlation with outcome as assessed at 3 months post-ictus. No statistically significant correlation was found between blood or CSF FPA levels and any of the other variables studied.     

Papaverine angioplasty to treat cerebral vasospasm following traumatic subarachnoid haemorrhage

The management of vasospasm associated with traumatic subarachnoid haemorrhage presents many challenges. We present a 20-year-old male admitted after sustaining a closed head injury complicated by a Fisher grade III traumatic subarachnoid haemorrhage. Despite treatment with intravenous nimodipine he developed a delayed ischaemic neurological deficit due to cerebral arterial vasospasm. The vasospasm was successfully managed with serial papaverine angioplasty.     

蛛网膜下腔出血并发脑血管痉挛基因多态性研究进展

背景 脑血管痉挛(cerebral vasospasm,CVS)是蛛网膜下腔出血(subarachnoid haemorrhage,SAH)的主要并发症,也是造成患者死亡和致残的主要原因.目前国内外较少涉及SAH并发CVS基因多态性领域的研究. 目的 人类对CVS基因多态性的深入研究,将会给我们在对这种灾难疾病的认识、识别和管理带来很多的好处. 内容 综述国内外对SAH后并发CVS基因多态性研究及其应用. 趋向 基因多态性及表达产物既可作为CVS发生的危险因子,又可以提示CVS治疗的预后,同时也可以为SAH后CVS的治疗提供新的靶点.     

Prostacyclin treatment normalises the MCA flow velocity in nimodipine-resistant cerebral vasospasm after aneurysmal subarachnoid haemorrhage

Background  Cerebral vasospasm triggered by subarachnoid haemorrhage is one of the major causes of post-haemorrhage morbidity and mortality. Several treatment modalities have been proposed, and none of them are fully effective. Methods  In this study we treated five patients with prostacyclin suffering vasospasm after a ruptured aneurysm not responding to high i.v. doses of nimodipine. All patients were severely ill, unconscious and in need of intensive care. Findings  A low dose of prostacyclin i.v. infusion for 72 h reversed the vasospasm as measured by transcranial Doppler technique. The mean MCA blood flow velocity decreased from 199 ± 31 cm/s to 92 ± 6 cm/s within 72 h after the start of the prostacyclin infusion. Conclusions  We suggest that low-dose prostacyclin treatment, an old treatment strategy, can be a treatment option in patients with vasospasm not responding to ordinary measures.     

Angiographic investigation of cerebral vasospasm in subarachnoid haemorrhage due to arteriovenous malformation

Summary Fifty (50) selected patients with arteriovenous malformation (AVM) with and without subarachnoid haemorrhage (SAH) were investigated, in respect of occurrence and course of the vasospasm. The diameters of the carotid siphon and its main branches were measured and plotted against the time elapsing between the haemorrhage and the angiographic study. Patients without SAH were used as a reference group. The results suggest intracranial arterial spasm to occur between the third and eleventh day after the onset of SAH. Patients with intracerebral haematoma may show vasospasm from the first day onwards. It seems that the radiologically demonstrated spasm in AVM had no impact on the clinical outcome in this series.     

Observer variability in assessment of angiographic vasospasm after aneurysmal subarachnoid haemorrhage

Summary In clinical practice and in many reported studies about incidences and time courses of vasospasm the angiographic spasms are judged by eye without clear definition of vessel narrowings. To evaluate the reliability of this diagnostic method two experienced neuroradiologists and two experienced neurosurgeons independently in two sessions, examined 30 carotid angiograms performed after an aneurysmal subarachnoid haemorrhage. The intra- and inter-observer agreements for the absent/present and localization diagnosis of vasospasm were calculated by means of Kappa statistics. Kappa values for both intra- and inter-observer agreement showed great variability and in general most of the agreements were not much better than chance expected agreement. The diagnostic method of judging angiographic vasospasm by eye without clear-cut definitions of vessels narrowings is unreliable and should not be used in the future, neither in clinical practice nor in research.     

Leflunomide prevents vasospasm secondary to subarachnoid haemorrhage

Summary Background. Though cerebral vasospasm is one of the most serious complications of subarachnoid haemorrhage (SAH), its complex pathogenesis is poorly understood and available clinical treatment options are unsatisfactory. This study was designed to examine the efficacy of leflunomide, an immunomodulatory agent with inhibitory properties, on vascular smooth muscle cell proliferation and inflammation in a rabbit cerebral vasospasm model. Methods. Twenty-two adult New-Zealand rabbits were assigned to 4 groups: control, SAH, SAH plus vehicle, SAH plus leflunomide. Subarachnoid haemorrhage was induced by administration of 1 ml of fresh unheparinised autologous arterial blood into the cisterna magna. Oral leflunomide (2 mg/kg) or vehicle treatment was started 12 h after the induction of subarachnoid haemorrhage and administered once a day. Three days later, the animals were sacrificed and the basilar artery was examined histologically for the lumen area and the thickness of the vessel wall. Inflammatory reaction was also examined by counting white blood cells within the vessel wall by means of light microscopic examination using haematoxylin and eosin staining. Findings. Severe and moderate vasospasms were detected in the basilar artery of the SAH and SAH plus vehicle treated groups, respectively. Leflunomide effectively reduced the vasospasm of the basilar artery. Compared to the vehicle treated group, leflunomide significantly reduced the lumen area (p < 0.01) and hyperplasia of the vessel wall (p < 0.01). Although inflammatory response within the vessel wall was reduced in the leflunomide treated group, no statistical significance was found between groups (p = 0.07). Conclusion. This study demonstrates for the first time that leflunomide treatment attenuates cerebral vasospasm in a rabbit SAH model while inflammatory reaction in the vessel wall is not affected. Although further studies are needed to reveal its molecular mechanisms in relieving vasospasm, leflunomide may provide a therapeutic potential for human cerebral vasospasm induced by SAH.     

HLA-type of cerebral vasospasm patients after aneurysmal subarachnoid hemorrhage

We studied human lymphocyte antigen (HLA) types in a group of 45 patients who had aneurysmal subarachnoid hemorrhage (SAH). A significantly increased frequency of HLA antigen A31 and a significantly decreased frequency of HLA antigen B40 were found. In patients with delayed ischemic neurological deficit (DIND) following aneurysmal SAH and HLA typing, HLA-Bw60 antigen showed significant increases; in patients who did not develop HLA-Aw33 and-Cw4 antigens showed significant. Among the patients with Fisher's Group 3 on CT, in particular, these antigens significantly increased when compared with controls from the same geographic area. These results suggest that HLA-Bw60 antigen plays a role as a predisposing factor of DIND resulting from vasospasm following aneurysmal SAH, and that HLA-Aw33 and-Cw4 exert protective influence against DIND.