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

Abstract

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.

Keywords: ACA = anterior cerebral artery; BA = basilar artery; BP = blood pressure; CBF = cerebral blood flow; CCT = cranial computed tomography; CVS; CVS = cerebral vasospasm; DIND; DIND = delayed ischemic neurological deficit; DSA = digital subtraction angiography; GCS = Glasgow Coma Scale; HES = hydroxyethyl starch; HH = Hunt and Hess; ICA = internal carotid artery; ICP = intracranial pressure; MAP = mean arterial blood pressure; MCA = middle cerebral artery; MTG = molsidomine treatment group; NO; NO = nitric oxide; SAH = subarachnoid hemorrhage; STG = standard therapy group; TCD = transcranial Doppler; VA = vertebral artery; mNIHSS = modified National Institutes of Health Stroke Scale; mRS = modified Rankin Scale; molsidomine; subarachnoid hemorrhage; vascular disorders; vasospasm.