Effectiveness comparisons of drug therapies for postoperative aneurysmal subarachnoid hemorrhage patients: network meta­analysis and systematic review.

OBJECTIVE: To compare the effectiveness of various drug interventions in improving the clinical outcome of postoperative patients after aneurysmal subarachnoid hemorrhage (aSAH) and assist in determining the drugs of definite curative effect in improving clinical prognosis. METHODS: Eligible Randomized Controlled Trials (RCTs) were searched in databases of PubMed, EMBASE, and Cochrane Library (inception to Sep 2020). Glasgow Outcome Scale (GOS) score, Extended Glasgow Outcome Scale (GOSE) score or modified Rankin Scale (mRS) score was used as the main outcome measurements to evaluate the efficacy of various drugs in improving the clinical outcomes of postoperative patients with aSAH. The network meta-analysis (NMA) was conducted based on a random-effects model, dichotomous variables were determined by using odds ratio (OR) with 95% confidence interval (CI), and a surface under the cumulative ranking curve (SUCRA) was generated to estimate the ranking probability of comparative effectiveness among different drug therapies. RESULTS: From the 493 of initial citation screening, forty-four RCTs (n = 10,626 participants) were eventually included in our analysis. Our NMA results showed that cilostazol (OR = 3.35,95%CI = 1.50,7.51) was the best intervention to improve the clinical outcome of patients (SUCRA = 87.29%, 95%CrI 0.07-0.46). Compared with the placebo group, only two drug interventions [nimodipine (OR = 1.61, 95%CI 1.01,2.57) and cilostazol (OR = 3.35, 95%CI 1.50, 7.51)] achieved significant statistical significance in improving the clinical outcome of patients. CONCLUSIONS: Both nimodipine and cilostazol have exact curative effect to improve the outcome of postoperative patients with aSAH, and cilostazol may be the best drug to improve the outcome of patients after aSAH operation. Our study provides implications for future studies that, the combination of two or more drugs with relative safety and potential benefits (e.g., nimodipine and cilostazol) may improve the clinical outcome of patients more effectively.

Anterior Temporal Approach for Clipping of Upper Basilar Artery Aneurysms: Surgical Techniques and Treatment Outcomes.

BACKGROUND: Upper basilar artery (BA) aneurysms, which consist of basilar tip and BA-superior cerebellar artery aneurysms, are challenging to treat with microsurgical clipping. The anterior temporal approach is one surgical approach used to treat aneurysms in this region. Most previous reports on this approach have consisted of unruptured cases. Assessing mostly ruptured cases in this study, we describe the surgical technique, patient characteristics, and surgical outcomes. METHODS: Twenty-three patients with aneurysms arising from the upper BA who received aneurysm clipping via an anterior temporal approach between December 2015 and January 2019 were retrospectively evaluated. RESULTS: The location of the aneurysms was the basilar tip in 15 patients (65.2%) and the BA-superior cerebellar artery junction in 8 patients (34.8%). Twenty-one patients (91.3%) presented with subarachnoid hemorrhage. Good outcomes (modified Rankin Scale score 0-2) at 3 months were achieved in 55.6% of all patients and in 80% of good-grade patients (World Federation of Neurosurgical Societies grades I-III) and patients with unruptured aneurysms. For patients with subarachnoid hemorrhage, a good outcome was achieved in 75% of good-grade patients. Postoperative transient oculomotor nerve palsy and thalamic infarctions were detected in 7 patients (30.4%) and 2 patients (8.7%), respectively. CONCLUSIONS: With appropriate case selection, the anterior temporal approach was effective and safe for clipping of upper BA aneurysms, especially under subarachnoid hemorrhage conditions.

Efficacy of fasudil for the treatment of aneurysmal subarachnoid hemorrhage: A systematic review protocol of randomized controlled trial.

BACKGROUND: This study aims to systematically assess the efficacy and safety of fasudil for the treatment of aneurysmal subarachnoid hemorrhage (ASH). METHODS: This study will include all of randomized controlled trials on the efficacy and safety of fasudil for the treatment of ASH. Ten electronic databases of PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Ovid, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched from inception to the May 1, 2019 without language restrictions. We will also search gray literatures to avoid missing any other potential studies. Two authors will independently perform study selection, data extraction and management, and methodologic quality assessment. The primary outcome is limbs function. The secondary outcomes comprise of muscle strength, muscle tone, quality of life, and adverse events. RESULTS: This study will provide a comprehensive literature search on the current evidence of fasudil for the treatment of ASH from primary and secondary outcomes. CONCLUSION: The results of this study will present evidence to determine whether fasudil is an effective and safety treatment for patients with ASH. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019136215.

Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping.

BACKGROUND: Cowden syndrome is characterized by multiple hamartomas and accompanied by a germline mutation of the phosphatase and tensin homolog gene. Cowden syndrome has been described to be associated with vascular anomalies such as arteriovenous malformation and developmental venous anomalies with high frequency. However, the association of cerebral aneurysms with this syndrome has not been reported yet. CASE DESCRIPTION: A 39-year-old Japanese man presented with a subarachnoid hemorrhage due to a ruptured giant fusiform middle cerebral artery aneurysm. We diagnosed him with Cowden syndrome by clinical presentations as outlined in the National Comprehensive Cancer Network's criteria. As the ruptured fusiform aneurysm involved a middle cerebral artery bifurcation, we prepared for extracranial-intracranial bypass surgery. We successfully performed a surgical clipping using multiple tandem clipping techniques and suction decompression techniques. Bypass surgery was not performed as reconstruction of the M2 trunks was successfully completed. CONCLUSIONS: We present this rare case that potentially indicates an association between cerebral aneurysms and Cowden syndrome. Because vascular anomalies are not included in the diagnostic criteria for Cowden syndrome, intracranial vascular anomalies may be underestimated. We therefore recommended a careful search of vascular diseases, including cerebral aneurysms, in cases of Cowden syndrome.

Coffee and tea consumption and the risk for subarachnoid hemorrhage: A meta-analysis.

OBJECTIVES: Reports on the association between coffee or tea consumption and subarachnoid hemorrhage (SAH) risk are inconsistent. The aim of this study was to determine if an association exists between consumption of coffee or tea and the risk for SAH. METHODS: A random-effects model was used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity among studies was assessed using the statistics Cochran's Q and I2. Seven studies on coffee consumption and five on tea consumption were included in the meta-analysis. RESULTS: The pooled RRs of SAH for the highest versus the lowest categories of coffee and tea consumption were 1.31 (95% CI, 0.84-2.05) and 0.83 (95% CI, 0.65-1.08), respectively. There was evidence of heterogeneity among studies of coffee consumption (Pheterogeneity = 0.002, I2 = 71.7%) but not among studies of tea consumption (Pheterogeneity = 0.34, I2 = 11.3%). Omitting one study that substantially contributed to the heterogeneity among studies of coffee consumption yielded a pooled RR of 1.51 (95% CI, 1.10-2.06). Dose-response analysis showed that the summary RRs of SAH for an increase of one cup of coffee and tea consumption per day were 1.00 (95% CI, 0.96-1.04) and 0.97 (95% CI, 0.85-1.11), respectively. There was no evidence of publication bias. CONCLUSION: Our meta-analysis of current evidence does not support an association between the consumption of coffee or tea and SAH risk. Further studies with prospective designs that control for important confounders and provide sufficient data for dose-response analysis are warranted.

A rare case of ruptured aneurysm of the paramedian artery of Percheron.

Introduction The artery of Percheron is a rare anatomic variant supplying bilateral medial thalamic nuclei and a variable portion of the rostral part of midbrain. Case report A 48-year-old female with massive subarachnoid hemorrhage due to a ruptured aneurysm of the paramedian artery of Percheron presented to the emergency room. Because of significant risk of recurrent intracranial hemorrhage, it was decided to proceed with endovascular embolization of the aneurysm. The patient was ultimately sent to a rehabilitation center and her presenting neurologic deficits showed significant improvements in the weeks following endovascular embolization treatment. Discussion The paramedian artery of Percheron is a rare anatomic variant and subarachnoid hemorrhage due to aneurysm of this artery is exceedingly rare. This case underlines the importance of a correct evaluation of cerebral arterial anatomy in order to choose the best endovascular therapeutic approach, reduce complications, and optimize patient outcome.

Pharmacokinetic Modeling of Intra-arterial Nimodipine Therapy for Subarachnoid Hemorrhage-Related Cerebral Vasospasm.

PURPOSE: Intra-arterial (IA) administration of nimodipine has been shown to be an effective treatment for subarachnoid hemorrhage-related cerebral vasospasm. The concentrations achieved in cerebral arteries during this procedure, though, are unknown. Therefore, there are no clinical studies investigating dose-dependent effects of nimodipine. We aimed at providing a pharmacokinetic model for IA nimodipine therapy for this purpose. METHODS: A two-compartment pharmacokinetic model for intravenous nimodipine therapy was modified and used to assess cerebral arterial nimodipine concentration during IA nimodipine infusion into the internal carotid artery (ICA). RESULTS: According to our simulations, continuous IA nimodipine infusion at 2 mg/h and 1 mg/h resulted in steady-state cerebral arterial concentrations of about 200 ng/ml and 100 ng/ml assuming an ICA blood flow of 200 ml/min and a clearance of 70 l/h. About 85 % of the maximal concentration is achieved within the first minute of IA infusion independent on the infusion dose. Within the range of physiological and pharmacokinetic data available in the literature, ICA blood flow has more impact on cerebral arterial concentration than nimodipine clearance. CONCLUSION: The presented pharmacokinetic model is suitable for estimations of cerebral arterial nimodipine concentration during IA infusion. It may, for instance, assist in dose-dependent analyses of angiographic results.

Reversible cerebral vasoconstriction syndrome presenting as subarachnoid hemorrhage: A rare cause of postpartum seizure.

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare cerebrovascular disorder affecting large- and medium-sized arteries, occurring most commonly in young women. Thunderclap headache is the usual primary symptom; seizure is uncommon. During the postpartum period, seizure is a significant concern. The main causes of postpartum seizures are posterior reversible encephalopathy syndrome and cortical venous thrombosis; RCVS-related postpartum seizure is rare. Despite its rarity, its course may be fulminant, resulting in permanent disability or death if the diagnosis is delayed and treatment is not started promptly. We report an unusual case of RCVS presenting as a subarachnoid hemorrhage in a 31-year-old woman admitted for postpartum seizure.

Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Oral nimodipine is standard therapy for patients suffering an aneurysmal subarachnoid hemorrhage (aSAH). During a national drug shortage, nimodipine therapy was shortened from a 21-day course to a 14-day course at our institution. OBJECTIVE: The objective of this study was to compare neurological outcomes among patients who had previously received the standard duration of therapy compared with those who received a shortened duration as a result of the national drug shortage. METHODS: This retrospective cohort study evaluated adult patients receiving nimodipine for aSAH from January 2012 to August 2013. Neurological outcome, graded by Modified Rankin Scale (mRS) at hospital discharge, was compared between patients receiving a shortened course and those receiving the standard duration of nimodipine. RESULTS: A total of 199 aSAH patients were included in the analysis. There were 164 patients in the standard-duration and 35 patients in the shortened-duration group. Baseline patient severity of illness, assessed by SAPS II (Simplified Acute Physiology Score), and severity of aSAH, assessed by Fisher grade, and Hunt and Hess grade scores, did not differ between the treatment groups. A shortened duration of nimodipine was not associated with a higher risk of a poor neurological outcome defined by mRS (odds ratio = 1.85; 95% CI = 0.54-6.32; P = 0.32). Mortality rates were similar between the groups. CONCLUSIONS: A 14-day course of nimodipine therapy was not associated with worse neurological outcomes in aSAH patients at one institution. More studies are needed prior to recommending a shortened duration of nimodipine therapy in all aSAH patients.

Nimodipine Dose Reductions in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The incidence of cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) is reduced by oral nimodipine but acute effects of the drug may include a significant decrease in mean arterial blood pressure (MAP). A dose reduction or discontinuation of the drug is recommended if recurrent MAP drops occur. The aim of our study was to evaluate the frequency and clinical significance of nimodipine dose modifications in patients suffering from aSAH. METHODS: 270 patients were included in our retrospective analysis of consecutively collected data of patients suffering from aSAH. The local treatment protocol was in accordance to national and international guidelines. Nimodipine was intended to be applied orally with a dosage of 60 mg every 4 h. RESULTS: Only 43.6 % of patients eligible for vasospasm prophylaxis with nimodipine received the full daily dose of 60 mg every 4 h. In 28.6 %, the dose had to be reduced by 50 % due to a significant reduction in blood pressure after administration and/or high dose of catecholamines. In 27.7 % of patients, oral administration of the drug was discontinued for the same reason. Dose reduction and discontinuation occurred with a significantly higher frequency in patients in poor clinical condition. Application of the full nimodipine dosage decreased the risk of unfavorable clinical outcome in multivariate analysis (OR 0.895, p = 0.029). CONCLUSIONS: Our results show that dose reduction or discontinuation of nimodipine due to changes in MAP occur frequently in clinical routine and may be associated with unfavorable clinical outcome.

Curcumin, encapsulated in nano-sized PLGA, down-regulates nuclear factor κB (p65) and subarachnoid hemorrhage induced early brain injury in a rat model.

BACKGROUND: More and more evidence revealed early brain injury (EBI) may determine the final outcome in aneurismal subarachnoid hemorrhage (SAH) patients. This study is of interest to examine the efficacy of nano-particle curcumin (nanocurcumin), a diarylheptanoid, on a SAH-induced EBI model. METHODS: A rodent double hemorrhage model was employed. Nanocurcumin (75/150/300µg/kg/day) was administered via osmotic mini-pump post-SAH. CSF samples were collected to examine IL-1ß, IL-6, IL-8 and TNF-α (rt-PCR). Cerebral cortex was harvested for NF-κB (p50/p65) (western blot), caspases (rt-PCR) measurement. RESULTS: Nanocurcumin significantly reduced the bio-expression of NF-κB (p65), when compared with the SAH groups. The levels of IL-1ß and IL-6 were increased in animals subjected to SAH, compared with the healthy controls, but absent in the high dose nanocurcumin+SAH group. Moreover, the levels of TNF-α in the SAH groups were significantly elevated. Treatment with nanocurcumin (300µg/kg) reduced the level to the healthy control. The cleaved caspase-3 and -9a was significantly reduced in 300µg/kg nanocurcumin treatment groups (P<0.05). CONCLUSION: Treatment with nanocurcumin exerts its neuroprotective effect through the upward regulation of NF-κB (p65) and also reduced mitochondrion related caspase-9a expression. Besides, nanocurcumin decreased CSF levels of TNF-α and IL-1ß, which may contribute to the extrinsic antiapoptotic effect. This study shows promise to support curcuminin, in a nano-particle, could attenuate SAH induced EBI.

Treatment of subarachnoid hemorrhage.

Nontraumatic subarachnoid hemorrhage from intracranial aneurysm rupture presents with sudden severe headache. Initial treatment focuses on airway management, blood pressure control, and extraventricular drain for hydrocephalus. After identifying the aneurysm, they may be clipped surgically or endovascularly coiled. Nimodipine is administered to maintain a euvolemic state and prevent delayed cerebral ischemia (DCI). Patients may receive anticonvulsants. Monitoring includes serial neurologic assessments, transcranial Doppler ultrasonography, computed tomography perfusion, and angiographic studies. Treatment includes augmentation of blood pressure and cardiac output, cerebral angioplasty, and intra-arterial infusions of vasodilators. Although early mortality is high, about one half of survivors recover with little disability.

Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Cerebral hemorrhages in CADASIL: report of four cases and a brief review.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. However, cerebral microbleeds have been found in 31-69% of CADASIL patients. METHODS: We describe four unrelated CADASIL patients who had hemorrhagic strokes. We also briefly review the literature on intracerebral hemorrhage (ICH) in CADASIL. RESULTS: Three patients had a thalamo-capsular hemorrhage (age at onset: 54, 67, 77) and one of these had a second hemispheric cerebellar hemorrhage. Another patient experienced an interpeduncular cistern subarachnoid hemorrhage when he was 39. None of these patients was receiving antiplatelets, anticoagulants or statins at the time of hemorrhage; all were hypertensive. NOTCH3 gene analysis revealed mutations on exons 14, 22 (two patients presenting the same mutation), and 24. MRI signs of previous hemorrhages were present in all these patients. CONCLUSIONS: Hemorrhagic stroke can occur in CADASIL similarly to sporadic cerebral small vessel diseases; this finding expands the phenotype of the disease. A diagnosis of CADASIL should probably be considered also in patients with ICH. These data bear potential implications in terms of need of better control of risk factors, particularly hypertension, and raise relevant questions about the use of antiplatelets as prevention measures in CADASIL patients.

[Clinical observation on the prevention and treatment of perioperative delayed cerebrovasospasm in patients with aneurysmal subarachnoid hemorrhage by the comprehensive protocol of integrative medicine].

OBJECTIVE: To investigate the efficacy and safety of the comprehensive protocol of integrative medicine in preventing and treating perioperative delayed cerebrovasospasm (DCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Using a prospective randomized controlled trial design, 63 aSAH inpatients were assigned to the treatment group (31 cases, 24 treated by intervention treatment and 7 by craniotomy) and the control group (32 cases, 26 treated by intervention treatment and 6 by craniotomy). All patients were treated with basic therapy and nimodipine. Those in the treatment group additionally took naomai jiejing decoction No. 1 and No. 2. The incidence and the mortality of DCVS, re-bleeding, hydrocephalus were compared on the 180th day. The middle cerebral artery mean flow velocity (Vm), PI value, linde-gard index on day 1, 3, 7, and 14 were compared. The Chinese medicine syndrome score, NIHSS, and revised Rankin questionnaire on day 1, 14, and 180 were compared. RESULTS: The DCVS occurred in 9 cases (29. 0%) of the treatment group and 17 patients (53.1%) of the control group, showing statistical difference (P < 0.05). The occurrence of re-hemorrhage was obviously lower in the treatment than in the control group (3.2% vs. 6.2%), showing statistical difference (P < 0. 05). There was no statistical difference in the mortality (6.4% vs. 9.4%) or the occurrence of hydrocephalus (29.0% vs 25.0%, P > 0.05). The Vm, PI, and linde-gard index on day 7, the Vm and linde-gard index on day 14 were obviously lower in the treatment group than in the control group (P < 0.05). The Chinese medicine syndrome score and NIHSS on day 14 and 180 were lower in the treatment group than in the control group, showing statistical difference (P < 0.05). CONCLUSION: The comprehensive protocol of integrative medicine could reduce the incidence of aSAH patients' DCVS, the Chinese medicine syndrome score and NIHSS, and improve their clinical symptoms.

Adverse events following acupuncture: a systematic review of the Chinese literature for the years 1956-2010.

OBJECTIVES: The objective of this study was to make non-Chinese readers better informed about the current safety situation of acupuncture in China. METHODS: Four (4) major Chinese comprehensive databases were searched: Chinese Journal Full-text Database (1949-2010), China Biomedical Literature Database (1978-2010), Chinese Technology Journal Database (1989-2010), and Wanfang (1998-2010). Case reports of adverse events related to acupuncture therapy were included. Literature reviews, case-control study, translations, duplicate literatures in various databases, and duplicate published articles with duplicate data were excluded. RESULTS: One hundred and sixty-seven (167) articles were included with 1038 cases, among which 35 patients died. The most frequent adverse events were syncope (468 cases), pneumothorax (307 cases), and subarachnoid hemorrhage (64 cases). CONCLUSIONS: Acupuncture-related adverse events were mainly caused by mental tension of the patient, improper operation by the doctor, and incompleteness of sterilization. Most of them can be avoided by standardizing teaching and clinical practices. Making the corresponding safety standards can greatly lower the risk of adverse events and protect patient safety to the greatest extent.

Endovascular treatment: balloon angioplasty versus nimodipine intra-arterial for medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) accounts significant morbimortality after aneurysmal subarachnoid hemorrhage. The objective of this study was to compare the clinical outcome of patients with CV treated by 2 endovascular procedures: intra-arterial nimodipine angioplasty (IANA) and balloon angioplasty (BA). Between 2008 and June 2011, we performed 22 IANA and 8 BA in 30 patients. The mean age was 44 years and 60% was female. In 17 patients, the treatment was clipping, whereas 13 underwent coil treatment. The CV was severe in 63%, moderate in 30%, and mild in 7%. Good outcome between 2 groups was similar (P = .36). The clinical outcome according to the subgroups of CV severity and modality treatment was equivalent (P = .22). Mortality at 3 months was 16% and 20% at 1 year. We did not find differences in the clinical outcome despite the fact that both techniques produce adequate angiographic resolution of CV.

A pilot study in acute subarachnoid haemorrhagic patients after aneurysm clipping with complementary therapies of Chinese medicine.

OBJECTIVES: Acute subarachnoid haemorrhage still has high mortality and morbidity despite the use of modern standard treatment. In Taiwan, complementary therapies of Chinese medicine are usually used to treat stroke patients. The aim of this study was to investigate the effect of complementary therapies of Chinese medicine on patients with acute subarachnoid haemorrhage after aneurysm clipping. DESIGN: This study was designed as a pilot study. A total of 32 patients with acute subarachnoid haemorrhage were randomly assigned to either a Chinese herbs extra group (CH) in which the patients were given complementary therapies of Chinese medicine and standard treatment, or a standard treatment only group (ST) in which patients were given standard treatment only. MAIN OUTCOME MEASURES: Glasgow Outcome Scale scores, which were assessed by an evaluator who was blinded to the groups, 3 months after admission, and total admission days including intensive care unit stay days. RESULTS: The average Glasgow Outcome Scale score 3 months after admission was 3.7±1.4 in the CH was greater than 3.0±1.7 in the ST (p=0.041). Average total admission days were 53.9±28.6 (median 61) in the ST longer than 28.1±19.1 (median 20.5) in the CH (p=0.004). CONCLUSION: Traditional Chinese medicine for the treatment of patients with acute subarachnoid haemorrhage is of value because they can increase Glasgow Outcome Scale scores 3 months after admission and also because they can reduce total admission days.

Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, clinical study.

OBJECTIVE: To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Neurosurgical intensive care unit of a University hospital. INTERVENTIONS: One hundred ten patients were randomized to receive intravenous magnesium sulfate or to serve as controls. Magnesium treatment was started with a bolus of 16 mmol, followed by continuous infusion of 8 mmol/hr. Serum concentrations were measured every 8 hrs, and infusion rates were adjusted to maintain target levels of 2.0-2.5 mmol/L. Intravenous administration was continued for 10 days or until signs of vasospasm had resolved. Thereafter, magnesium was administered orally and tapered over 12 days. MEASUREMENTS AND MAIN RESULTS: Delayed ischemic infarction (primary end point) was assessed by analyzing serial computed tomography scans. Transcranial Doppler sonography and digital subtraction angiography were used to detect vasospasm. Delayed ischemic neurologic deficit was determined by continuous detailed neurologic examinations; clinical outcome after 6 months was assessed using the Glasgow outcome scale. Good outcome was defined as Glasgow outcome scale score 4 and 5.The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209). Delayed ischemic neurologic deficit was nonsignificantly reduced (9 of 54 vs. 15 of 53 patients; p = .149) and transcranial Doppler-detected/angiographic vasospasm was significantly reduced in the magnesium group (36 of 54 vs. 45 of 53 patients; p = .028). Fewer patients with signs of vasospasm had delayed cerebral infarction. CONCLUSION: These data indicate that high-dose intravenous magnesium can reduce cerebral ischemic events after aneurysmal subarachnoid hemorrhage by attenuating vasospasm and increasing the ischemic tolerance during critical hypoperfusion.