Efficacy of Acupuncture Treatment to Prevent Cerebral Vasospasm After Subarachnoid Hemorrhage: A Double-Blind, Randomized Placebo-Controlled Trial.

Objectives: To investigate the efficacy of acupuncture in preventing cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) and explore its underlying mechanism. Design: A randomized, double-blinded, and placebo-controlled trial. Setting/Location: Subjects were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea Subjects: A total of 50 patients admitted with acute SAH. Interventions: The study group received acupuncture treatments (n = 25), while the control group underwent mock transcutaneous electrical nerve stimulation and sham acupuncture (n = 25) six times/week for 2 weeks. Outcome measures: The primary outcome was the incidence of delayed ischemic neurologic deficit (DIND), and secondary measurements included angiographic vasospasm, vasospasm-related infarction, modified Rankin Scale score, and plasma nitric oxide (NO) and endothelin-1 (ET-1) levels. Results: The study group treated with acupuncture showed a lower incidence of DIND (9.1%) than the control group (20.8%); however, this difference in the incidence of DIND was not statistically significant. The study group demonstrated better clinical outcomes, especially in functional recovery. Significant alterations in plasma NO and ET-1 levels after the 2-week intervention were observed only in the study group. Conclusions: Their study shows that acupuncture treatment improved functional recovery after SAH and could potentially prevent cerebral vasospasm. These effects could be attributed to the recovery of endothelial dysfunction by acupuncture through modulating the plasma NO and ET-1 levels. The study protocol has been registered on www.clinicaltrials.gov (NCT02275949).

Cisternal lavage via third ventriculostomy through the fenestrated lamina terminalis after aneurysm clipping: Technical note.

Delayed cerebral infarction (DCI) contributes to the burden of morbidity and mortality acquired by patients with aneurysmal subarachnoid hemorrhage (SAH). Cisternal lavage may prevent DCI. Delivery of lavage therapy to the basal cisterns, however, is challenging. Here, we report a novel method for the delivery of cisternal lavage using a cisterno-ventricular catheter (CVC) inserted via the fenestrated lamina terminalis during aneurysm clipping. In two high-risk aSAH patients a CVC was inserted into the third ventricle through the fenestrated lamina terminalis during aneurysm clipping. Post-operatively, continuous cisternal lavage using Urokinase or Nimodipine was applied using an external ventricular drain (EVD) as inflow tract and the CVC as outflow tract. Neurological outcome at 6 months was assessed by modified Rankin scale. Catheter placement into the third ventricle through the fenestrated lamina terminalis was performed without complications. Application of a free-running electrolyte solution containing Urokinase or Nimodipine via the EVD and drainage via the CVC was feasible. Cisternal Nimodipine application normalized sonographic vasospasm in both cases. DCI did not occur. CVC placement for ventriculo-cisternal lavage may represent a useful method for DCI prevention. It can be considered in aSAH patients at risk for DCI if the chiasmatic region is accessed during aneurysm clipping.

Prevention and Treatment of Hyponatremia in Patients with Subarachnoid Hemorrhage: A Systematic Review.

BACKGROUND: Current guidelines for the management of hyponatremia in patients with subarachnoid hemorrhage (SAH) are not based on a systematic assessment of the literature. We evaluated published studies on the efficacy and safety of current preventative and treatment strategies for hyponatremia in patients with SAH. METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and PubMed for relevant studies. Primary outcomes of interest included neurologic functional outcomes, symptomatic vasospasm, and others. Secondary outcomes included measures of sodium and volume status. RESULTS: We included 5 out of 117 identified studies: 1 before-and-after observational trial (using fludrocortisone) and 4 randomized controlled trials (2 using fludrocortisone; 2 using hydrocortisone). All 5 trials had a high risk of bias in at least 1 domain. We could not perform a meta-analysis of functional outcomes; however, individual studies did not demonstrate statistically significant differences. Mineralocorticoid use did not statistically significantly reduce the incidence of symptomatic vasospasm (relative risk, 0.60; 95% confidence interval, 0.35-1.03; I2 = 0%). The studies did not report other primary outcomes. In the 4 RCTs, mineralocorticoid use reduced natriuresis and volume contraction. CONCLUSIONS: Current evidence does not demonstrate a benefit of preventative treatment with mineralocorticoids in clinically important outcomes, although a difference cannot be ruled out due to imprecision. Larger well-designed trials are needed to establish the impact of mineralocorticoids and fluid and sodium supplementation strategies on clinically relevant outcomes in the prevention and treatment of hyponatremia in patients with SAH.

Effects on vessel measurement accuracy and subsequent occlusion after calcium channel blocker infusion during treatment of cerebral aneurysms with the Pipeline embolization device.

Introduction/Purpose To achieve aneurysm occlusion, flow diverters (FDs) must be accurately sized to maximize coverage over the neck and induce thrombosis. Catheterization for diagnostic angiography can cause vasospasm that may affect vessel measurements. This study evaluates impacts of intra-arterial infusion of a calcium channel blocker (CCB) on angiographic measurements in patients treated with FDs to determine effects on final diameter of the FD and subsequent occlusion. Materials and methods Pre-treatment measurements were recorded for diameter of the distal and proximal landing zones and maximum and minimum diameters between these segments. Post-treatment measurements of the stent following deployment were recorded at these locations. When CCB was infused, post-infusion pre-treatment measurements were recorded. Rates of occlusion were noted for all patients. T-tests were performed to assess for differences in pre- and post-treatment measurements and rates of occlusion between groups with and without CCB infusion. Results Twenty-eight FDs were deployed to treat 25 aneurysms in 24 patients. CCB infusion was performed prior to deployment of 12 (42.9%) devices. No significant difference was noted between groups for pre- and post-treatment measurement changes. Confirmed aneurysm occlusion was more likely to occur in the CCB infusion group (88.9% vs. 36.4%, p = 0.009). Conclusion Optimization of device sizing is important to increase FD density over the aneurysm neck and promote thrombosis. To improve measurement accuracy, CCB infusion can reduce effects of mild vasospasm. Subsequent aneurysm occlusion was more likely to occur following FD treatment when device size selection was based on measurements performed following CCB infusion.

ω-3 Fatty Acids Ethyl Esters Suppress Cerebral Vasospasm and Improve Clinical Outcome Following Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Occurrence of cerebral vasospasm after onset of aneurysmal subarachnoid hemorrhage (SAH) is a critical factor determining clinical prognosis. Eicosapentaenoic acid and docosahexaenoic acid, both ω-3 fatty acids (ω-3FA), can suppress cerebral vasospasm, and docosahexaenoic acid can relax vessel vasoconstriction and have neuroprotective effects. We investigated whether administration of ω-3FA prevented cerebral vasospasm occurrence and improved clinical outcomes after aneurysmal SAH. METHODS: From 2012 to 2015, 100 consecutive patients with aneurysmal SAH were divided into 2 periods. Between 2012 and 2013 (control period), 45 patients received standard management. Between 2014 and 2015 (ω-3FA period), 55 patients were prospectively treated with additional ω-3FA. Occurrence of cerebral vasospasm, occurrence of cerebral infarction caused by vasospasm, and modified Rankin Scale scores at 30 days and 90 days after onset of SAH for each period were evaluated and compared. RESULTS: The frequency of angiographic cerebral vasospasm in the ω-3FA period was significantly lower than in the control period (12 patients vs. 23 patients, P = 0.004). The frequency of new infarction caused by vasospasm in the ω-3FA period was also significantly lower than in the control period (5 patients vs. 14 patients, P = 0.011). There was a significant difference in modified Rankin Scale scores at 90 days after onset of SAH between the groups (P = 0.031). No adverse events were associated with ω-3FA administration. CONCLUSIONS: Administration of ω-3FA after aneurysmal SAH may reduce the frequency of cerebral vasospasm and may improve clinical outcomes.

Long-Term, Continuous Intra-Arterial Nimodipine Treatment of Severe Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm. METHODS: Ten patients were included with refractory macrovasospasm despite bolus nimodipine application (n = 4) or with primary severe vasospasm (n = 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour. RESULTS: The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved (n = 5) or disappeared (n = 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months. CONCLUSIONS: In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects.

Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

Glycyrrhizin Attenuates Proinflammatory Cytokines through a Peroxisome Proliferator-Activated Receptor-γ-Dependent Mechanism and Experimental Vasospasm in a Rat Model.

The peroxisome proliferator-activated receptor (PPAR) is downregulated in the cortex of experimental subarachnoid hemorrhage (SAH) animals. This study is to examine the effect of glycyrrhizin on the alternation of PPARs and proinflammatory cytokines in a rodent SAH model. CSF cytokines were evaluated by RT-PCR. Basilar arteries (BAs) were harvested to examine PPARs (RT-PCR and Western blot), and a morphological examination was conducted. Deformed endothelium and tortuous elastic lamina were observed in the BAs of the SAH groups, but they were absent in the glycyrrhizin groups or the healthy controls. The PPAR-γ and -δ protein levels were reduced in the SAH groups (p < 0.01). Glycyrrhizin significantly increased the expressed PPAR-γ protein and mRNA (preconditioning) and PPAR-δ mRNA (both treatment and preconditioning), which corresponded to the reduced IL-1ß and TNF-α levels. The administration of a PPAR-γ inhibitor, BADGE, halted the reduction of IL-1ß and TNF-α in the glycyrrhizin groups. Conclusively, glycyrrhizin exerts anti-inflammatory effects on SAH-induced vasospasm and attenuates the expression of PPARs, especially PPAR-γ, which corresponds to the severity of SAH-related inflammation. These findings also offer credit to the antivasospastic effect of glycyrrhizin and its vasculoprotective effect in animals subjected to SAH.

Intracranial biodegradable silica-based nimodipine drug release implant for treating vasospasm in subarachnoid hemorrhage in an experimental healthy pig and dog model.

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant.

Nimodipine for the prevention of cerebral vasospasm after subarachnoid hemorrhage in 12 children.

INTRODUCTION: Subarachnoid hemorrhage is a rare, but life-threatening neurological emergency. Cerebral vasospasm is a complication of subarachnoid hemorrhage that contributes significantly to morbidity and mortality. Nimodipine has been used in adults to reduce the incidence of cerebral vasospasm after subarachnoid hemorrhage and improve long-term outcomes. There are, however, no data in children. METHODS: Records of children with a confirmed diagnosis of subarachnoid hemorrhage who received nimodipine between January 1, 2005 and August 31, 2013 were reviewed. Dosing of nimodipine and associated hypotensive events were recorded. Transcranial Doppler ultrasonography, cranial computerized tomography, and angiography were followed as a measure of cerebral vasospasm, rebleeding, and subsequent infarction. RESULTS: Twelve children (average age 11.8 ± 3.3 years, age range 3.5 to 17.3 years) were included. Aneurysm was responsible for the highest percentage (41.7%) of subarachnoid hemorrhage events. The mean dose of oral nimodipine was 1 mg/kg every 4 hours and was associated with a high rate of hypotension requiring intervention or dose modification. Clinical outcomes while on nimodipine therapy varied; evidence of vasospasm was observed in 67%, new infarction in 33%, and rebleeding in 17%. Functional and cognitive deficits were minor in two-thirds and absent in the remaining individuals. All patients survived until hospital discharge. CONCLUSIONS: Oral nimodipine after subarachnoid hemorrhage in children does not eliminate vasospasm, rebleeding, or infarction and is associated with significant hypotension. Nevertheless, clinical outcomes appear favorable relative to the adult population who receive nimodipine. Further study, with dose titration, is warranted.

Cilostazol administration with combination enteral and parenteral nutrition therapy remarkably improves outcome after subarachnoid hemorrhage.

OBJECTIVE: In order to prevent cerebral vasospasm (VS) following aneurysmal subarachnoid hemorrhage (SAH), we introduced combined enteral nutrition (EN) and parenteral nutrition (PN) with oral cilostazol administration to the postoperative patient after SAH and investigated the effect on VS. METHODS: After aneurysmal SAH, 130 postoperative patients were enrolled in this study between April 2008 and March 2012. The patients enrolled before April 2010 were treated by conventional therapy (control group). The patients enrolled after April 2010 were administrated cilostazol 200 mg/day and received EN and PN simultaneously (combined group). RESULTS: The combined group consisted of 62 patients and the control group of 68 patients. Angiographic VS occurred in 33.9 % (n = 21) of the combined group and in 51.5 % (n = 35) of the control group (p = 0.051, Fisher exact test). The incidence of symptomatic VS was significantly lower in the combined group (p = 0.001). The incidence of new cerebral infarctions was also significantly lower in the combined group (p = 0.0006). Clinical outcome at discharge was also significantly better in the combined group than in control group (p = 0.031). CONCLUSIONS: Cilostazol administration with combination EN and PN is remarkably effective in preventing cerebral VS after aneurysmal SAH.

Removal of clots in subarachnoid space could reduce the vasospasm after subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a major cause of morbidity and mortality. We studied the effects of clot removal on multiple outcome variables following the clipping of ruptured anterior communicating aneurysms. METHODS: From 2007 to 2011, 30 patients with Fisher grade III aneurysmal SAH underwent clipping of an anterior communicating artery aneurysm before SAH day 3. There were 20 women and 10 men, mean age 53.4, range 28-80 years. Seventeen underwent fenestration of lamina terminalis and cisternal removal of clots (group A), and 13 did not (Group B). We compared clinical grades, presence of hydrocephalus at admission, treatment modality, occurrence of clinical vasospasm, the need for interventional vasospasm therapy, and need for ventriculoperitoneal shunting. FINDINGS: Vasospasm affected 5 of 17 (29%) in group A and 8 of 13 (61.5%) in group B (p < 0.05). Endovascular treatment for vasospasm was required in one patient in group A (5.8% of 17, 20% of 5) and in five from group B (38.4% of 13, 62.5% of 8) (p < 0.05). Mortality was observed in one case in group A (5.8% of 17, 20% of 5) and in two cases in group B (15.3% of 13, 25% of 8) and was related to vasospasm after SAH. Ventriculoperitonal shunt (VPS) was required in one case in group A (5.8%) and in five cases in group B (38.4%). CONCLUSIONS: Fenestration of the lamina terminalis and removal of cisternal clots significantly decreased the incidence of post-SAH hydrocephalus and was associated with better outcomes in our series.

Surgical treatment of ruptured anterior circulation aneurysms: comparison of pterional and supraorbital keyhole approaches.

BACKGROUND: Recent advancements in microsurgical techniques and instrumentation have allowed the development of the keyhole approach in aneurysm surgery. OBJECTIVE: To compare the safety, efficacy, and 1-year clinical outcome of supraorbital keyhole and standard pterional approaches for ruptured anterior circulation aneurysms. METHODS: A total of 87 patients underwent surgical clipping, 40 through the pterional and 47 through the supraorbital keyhole approach. Baseline demographics, operative time, procedural complications, and 1-year patient outcome were retrospectively compared. RESULTS: The 2 groups were comparable with respect to baseline characteristics, with the exception of a higher proportion of small aneurysms (<7 mm) in the supraorbital group (70.2% vs. 37.5%, P = .002). Total operative time was significantly shorter in the supraorbital group (205 minutes, P < .001) compared with the pterional group (256 minutes). The rate of procedural complications was lower in patients treated through the pterional (17.5%) vs the supraorbital approach (23.4%, P = .4). Intraoperative aneurysm ruptures occurred more frequently in the supraorbital group (10.6% vs. 2.5%). No patient experienced early or late rebleeding in either group. One year after treatment, 75% (30/40) of patients achieved a favorable outcome (Glasgow outcome scale IV or V) in the pterional group vs 76.6% (36/47) in the supraorbital group (P = .8). CONCLUSION: The rate of procedural complications may be higher with the supraorbital keyhole approach, but overall patient outcomes appear to be comparable. The pterional approach is a simple, reliable, and efficient procedure. The keyhole approach may be an acceptable alternative for neurosurgeons who have gained sufficient experience with the technique, especially for small noncomplex aneurysms.

Thunderclap headache triggered by micturition: responsive to nimodipine.

Primary thunderclap headache (TCH) is a rare condition, of which the onset can be triggered by coughing, exercise, and sexual activity. Micturition is a recognized trigger of secondary TCH with pheochromocytoma in bladder, but not of primary TCH. We describe a patient with an apparent primary TCH, which repeatedly occurred immediately after micturition until she achieved a therapeutic dosage of nimodipine.

Medidas protectoras frente a la isquemia cerebral tras hemorragia subaracnoidea (I) / Protective measures against cerebral ischemia following subarachnoid hemorrhage: part 1

Objetivos: La presencia de vasoespasmo cerebral tras hemorragia subaracnoidea aneurismática contribuye a la importante morbimortalidad de esta entidad. Por ello, se han desarrollado múltiples estudios con diferentes tratamientos dirigidos a su prevención, aunque la evidencia sobre su eficacia es limitada. Nuestro objetivo fue realizar una revisión bibliográfica de las diferentes terapias con evidencia científica para la prevención del vasoespasmo cerebral posthemorragia subaracnoidea aneurismática. Métodos: Búsqueda en MEDLINE (desde 1950 hasta octubre 2009) y revisión bibliográfica de las publicaciones halladas sobre prevención del vasoespasmo cerebral posthemorragia subaracnoidea aneurismática. Se restringió la búsqueda a artículos en inglés, francés y español. Se emplearon las palabras clave [cerebral vasospasm, subarachnoid hemorrhage, therapy, nimodipine, triple h, clazosentan, statins, magnesium] y sus combinaciones. Además se llevó a cabo una búsqueda manual en las referencias de los artículos seleccionados. Se incluyeron artículos que reunieran las siguientes condiciones: estudios controlados aleatorizados, metaanálisis, estudios clínicos no aleatorizados, estudios descriptivos, estudios analíticos observacionales, artículos de opinión y revisión. Resultados: La parte 1 analiza el tratamiento con calcioantagonistas y la triple terapia (hipertensión, hemodilución e hipervolemia) y la parte 2 analiza nuevas terapias como son el clazosentán, el magnesio y las estatinas. Hallamos 597 referencias de las cuales 283 fueron seleccionadas. Se incluyeron finalmente 61, las cuales se distribuyeron en 2 artículos de opinión, 21 estudios controlados aleatorizados, 22 artículos de revisión, 3 metaanálisis, 4 estudios clínicos no aleatorizados, 1 estudio descriptivo y 5 estudios analíticos observacionales. Tres estudios (2 metaanálisis y un estudio controlado aleatorizado) demostraron un beneficio en términos de morbimortalidad del uso del nimodipino en pacientes con hemorragia subaracnoidea aneurismática. Por el contrario en el análisis del resto de fármacos (clazosentán, estatinas y magnesio) no se objetivó un beneficio clínico estadísticamente significativo. Conclusiones: En la actualidad no hay suficiente evidencia para apoyar la utilización de triple terapia, clazosentán, estatinas y sulfato de magnesio para la prevención del vasoespasmo cerebral posthemorragia subaracnoidea aneurismática. El único tratamiento preventivo recomendado es el nimodipino(AU)

Background and objectives: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage contributes significantly to morbidity and mortality. Many studies on the various treatments aimed at preventing cerebral vasospasm have been carried out, but evidence of efficacy is limited. Our aim was to review the literature on the various therapies for which there is scientific evidence of protection against cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Methods: MEDLINE search (1950 to the october 2009) and review of articles found on the prevention of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. The search was restricted to articles in English, French, and Spanish. The keywords were cerebral vasospasm, subarachnoid hemorrhage, therapy, nimodipine, triple H, clazosentan, statins, and magnesium in addition to the word forms derived from them. We also searched manually for references cited in the selected articles. A title was included if it was a randomized controlled trial, meta-analysis, nonrandomized clinical trial, descriptive study, observational study with statistical analysis, opinion article, or expert review. Results: Part 1 analyzed treatment with calcium antagonists and triple-H therapy (hypertension, hemodilution, and hypervolemia). Part 2 analyzed new therapies such as clazosentan, magnesium, and statins. A total of 597 titles were located; 283 were initially selected. The 61 articles finally selected for review were of the following types: 2 opinion articles, 21 randomized controlled trials, 22 expert review articles, 3 meta-analyses, 4 nonrandomized clinical trials, 1 descriptive study, and 5 observational studies with statistical analysis. Three studies (2 meta-analyses and 1 randomized controlled trial) demonstrated that nimodipine use confers benefits (reduced morbidity and mortality) for patients with aneurysmatic subarachnoid hemorrhage. Statistically significant clinical benefits ould not be demonstrated for the other drugs (clazosentan, statins, and magnesium). Conclusions: Insufficient evidence is available to support the use of the triple-H therapy, clazosentan, statins, or magnesium sulfate for the prevention of cerebral vasospasm following subarachnoid hemorrhage. Nimodipine is the only preventative treatment that can be recommended(AU)

[Effects of nimodipine on rabbits with symptomatic cerebral vasospasm].

OBJECTIVE: To investigate the effects of nimodipine on symptomatic cerebral vasospasm in rabbits. METHODS: Twenty four japanese white rabbits which ligation of bilateral common carotid arteries and no neurological deficits were randomized to sham-operation, subarachnoid hemorrhage (SAH) and nimodipine which injected of nimodipine 0.1 mg/kg, continuous vein administration 5 day. The behavior scores, neurological scores were observed everyday and cerebral angiography changes were measured twice by 3D-CTA, and basilar artery was removed for pathological examination after last CTA examination. RESULTS: In SAH group, The basilar artery were significantly vasoconstrictive on 5 days, neurological scores were increased, and the basilar artery was found apoptosis-like changes under light microscopic and electron microscope. Nimodipine group could not dilated the basilar artery arteriospasm after SAH, but it could attenuate neurological deficit, and obviously alleviate the pathological changes of basilar artery. CONCLUSION: Nimodipine could not vasodilation of basilar artery in SCVS, but obviously could alleviate neurological changes and pathological changes of basilar artery in rabbits with symptomatic cerebral vasospasm.

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.

Preventive effects of intraperitoneal selenium on cerebral vasospasm in experimental subarachnoid hemorrhage.

Vasospasm is an important cause of morbidity and mortality with subarachnoid hemorrhage (SAH). The effect of intraperitoneal administration of selenium, which is an antioxidant on cerebral vasospasm was investigated in an experimental model. By means of intracisternal blood injection model, SAH was induced in 24 rabbits, which were randomly divided into 3 groups (group 1= control group, group 2=SAH alone group, and group 3=SAH plus selenium group). Basilar artery angiography was performed on day 0 and day 3 as described. Intraperitoneal selenium (0.05 mg/kg) treatment was started after the induction of SAH and administered once a day. Three days later, the animals were killed and the basilar artery was examined histologically for the luminal diameter and thickness of the arterial muscular wall. The mean values for the measurements of angiographic luminal diameter, pathologic luminal area, muscular wall thickness derived from the blind observer were analyzed statistically. There was no statistically significant difference in basal angiographic luminal diameter evaluation between groups 1-2-3 (P>0.005). But in third day angiography; comparison of group 2 and group 1-3 showed statistically significant differences (P<0.001). In pathologic investigation; there was statistically significant difference in luminal area and muscular wall thickness of the basilar artery between groups 1, 2, and 3 (P<0.005). Intraperitoneal selenium treatment was found effective by increasing the angiographic diameter; pathologic luminal area and reducing muscular wall thickness measurements. This is the first study to show that intraperitoneal administration of selenium is effective in preventing vasospasm after SAH in rabbits.