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.

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.

Comparison of intrathecal dotarizine and nimodipine treatments in cerebral vasospasm after subarachnoid hemorrhage: an experimental study in rabbits.

BACKGROUND: cerebral vasospasm (CVS) is one of the most considerable complications of subarachnoid hemorrhage (SAH). The aim of this study was to assess and to compare the ability of intrathecal dotarizine and nimodipine to prevent and treat vasospasm in a rabbit model of subarachnoid hemorrhage. METHOD: thirty male New Zealand white rabbits weighing 2,500-3,000 g were allocated into five groups randomly. The treatment groups were as follows: Control, only SAH, SAH/Dotarizine, SAH/Nimodipine, SAH/Vehicle. Forty-eight hours after SAH injection, all animals underwent femoral artery catheterization procedure by open surgery under anesthesia and angiography performed for each animal in the fifth day just before sacrifice. FINDINGS: basilar artery vessel diameters are measured by angiography. Basilar artery vessel diameters and luminal sectional areas are measured in pathology slides. There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). CONCLUSIONS: these findings demonstrate that calcium channel blocker dotarizine has marked vasodilatory effect in an experimental model of SAH in rabbits. Nimodipine is an effect-proven agent in CVS, but dotarizine may take place of it.

Continuous selective intraarterial infusion of nimodipine for therapy of refractory cerebral vasospasm.

BACKGROUND: For endovascular treatment of vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), an intraarterial treatment course with the calcium channel antagonist nimodipine infused for 30 min is proposed. As some patients still show ongoing vasospasm thereafter, we report on our experience with an extended time period of selective intraarterial nimodipine administration. METHODS: In nine patients with aSAH and refractory cerebral vasospasm, we left the catheter in place within the internal carotid artery after angiography. On the neurosurgical ICU, a continuous infusion of intraarterial nimodipine was commenced, combined with intraarterial heparin anticoagulation. Therapy was controlled with extended neuromonitoring techniques. RESULTS: Three patients died from refractory vasospasm and a fourth suffered lethal sepsis. Three patients survived in a good clinical condition, two of them without apparent neurologic deficit. The efficacy of intraarterial nimodipine was best verified with regional CBF monitoring. TCD failed to detect vasospasm in two patients and missed improvement in four. Brain tissue oxygenation increased in all patients, but was not indicative of vasospasm in one. CT perfusion reflected the treatment course adequately in the qualitative scans. CONCLUSION: Selective continuous intraarterial nimodipine treatment for refractory cerebral vasospasm after aSAH seems feasible and may add to the endovascular therapeutic options. Appropriate monitoring technology is essential for further investigation of this novel technique.

Intraventricular nicardipine for refractory cerebral vasospasm after subarachnoid hemorrhage.

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

Magnesium sulfate: role as possible attenuating factor in vasospasm morbidity.

BACKGROUND: Among the many complications of SAH, one of the most important is vasospasm. Several treatment alternatives have been proposed for this condition, with far-from-ideal results being obtained. Magnesium sulfate recently returned to the scene (with still unproven benefit) as an adjuvant in the treatment of vasospasm. METHODS: Seventy-two patients diagnosed with SAH by aneurysm rupture were submitted to microsurgery craniotomy and subdivided in 2 groups. Group 1, formed by 48 patients, received prophylactic hypervolemic and hemodilution therapy in addition to nimodipine. Group 2, composed of 24 patients, received the same treatment of group 1 with the addition of magnesium sulfate in continuous infusion from 120 to 150 mg a day, keeping serum magnesium levels close to double normal values. RESULTS: Age was 49 +/- 12.6 years. Ratio of female to male was 3.16:1. Most patients were admitted in a Hunt-Hess grade 2 (46.4%) and Fisher grade 3 (52.8%). Anterior communicating artery aneurysms were the most common in location (38.8%). Both groups were compared, and there was no statistical difference related to age, sex, and Glasgow, Fisher, or Hunt-Hess admission grades. No statistical difference in vasospasm incidence was found between the two groups. However, in group 1, vasospasm was correlated with a longer hospitalization time (P = .0003), different from group 2, in which patients with vasospasm receiving magnesium sulfate required less hospitalization time. CONCLUSION: Magnesium did not seem to interfere in vasospasm frequency but apparently acted favorably in decreasing morbidity and length of hospital stay.