Clinical Neurology and Neurosurgery 115 (2013) 400–404 Contents lists available at SciVerse ScienceDirect Clinical Neurology and Neurosurgery j o ur nal homep age: www.elsevier.com/locate/clineuro Evaluation of the intravenous magnesium sulfate effect in clinical improvement of patients with acute ischemic stroke  Daryoush Afshari a,∗ , Nasrin Moradian a , Mansour Rezaei b a Neurology Department of Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran b Kermanshah University of Medical Sciences, Kermanshah, Iran a r t i c l e i n f o Article history: Received 23 January 2012 Received in revised form 3 May 2012 Accepted 2 June 2012 Available online 30 June 2012 Keywords: Stroke Magnesium sulfate Neuroprotective a b s t r a c t Background: Evidence is mounting that magnesium may play a critical role in the development of strokes and the healing process during and after a stroke. Magnesium is an N-methyl-d-aspartate (NMDA) glu- tamate receptor antagonist that has been shown to be neuroprotective in many preclinical models of ischemic and excitotoxic brain injury. This study was performed to evaluate the intravenous magnesium sulfate effect in clinical improvement of patients with acute ischemic stroke. Methods: One hundred and seven patients with acute ischemic stroke signs and symptoms lasting less than 12 hours were included in the study and were divided into two groups, 55 patients received 4 g of MgSO 4 over 15 minutes and then 16 g over the next 24 hours, and 52 patients were received matching placebo. The study primary end point was stroke related neurologic deficit evaluation by the national institute of stroke scale (NIHSS). Results: Patients receiving MgSO 4 showed significant recovery compared with the group of patients receiving placebo. Conclusion: This study suggests that magnesium sulfate can be used as a safe and useful neuroprotective agent in acute ischemic stroke and lacunar stroke patients may represent a relevant and practical target population for agents with biological activity in white matter. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Cerebrovascular accident (CVA) is approximately 50% of the cause of neurological disorders that leading to admission of the patients in general hospitals [1]. Stroke is the leading cause of disability in adults. Worldwide, stroke is also a lead- ing cause of death, with stroke mortality being particularly high in Eastern Europe and Asia. The human and financial costs of stroke are immense, and its estimated annual eco- nomic impact on the United States, both directly in health care and indirectly in lost income, is approximately $41 billion [2]. The only currently approved medical stroke therapy, tissue plasminogen activator (tPA), is a thrombolytic that targets the thrombus within the blood vessel [3]. Neuroprotective agents, another approach to stroke treatment, have generated as much interest as thrombolytic therapies. Using various mechanisms,  This work was supported by the Vice-chancellor for research, Kermanshah Uni- versity of Medical Sciences and Health Services. ∗ Corresponding author. Tel.: +98 8318354529; fax: +98 8318354529. E-mail addresses: afshari d@yahoo.com (D. Afshari), moradiannasrin60@yahoo.com (N. Moradian). neuroprotective agents attempt to save ischemic neurons in the brain from irreversible injury [4]. Despite widespread interest in neuroprotective drug therapy and positive results in experimental animals, to date no neuropro- tective agent has been approved by the FDA for acute ischemic stroke [2]. Magnesium is NMDA glutamate receptor antagonist that is neuroprotective in many preclinical models of ischemic and excitotoxic brain injury [5–9]. There are a number of possible mech- anisms by which magnesium may act, including increased regional cerebral blood flow to ischemic brain areas [10], enhanced recovery of cellular energy metabolism after ischemia [11,12] and preven- tion of glutamate dependent necrosis in the hippocampal neurons [13]. Previous small clinical trials on the efficacy of MgSO 4 in improvement of acute stroke have shown no evidence of undesir- able neurological or cardiovascular effects [14,15]. Unlike the great majority of other neuroprotective agents, there is extensive clinical experience with magnesium, largely in pre-eclampsia/eclampsia and myocardial infarction, which confirm its safety and tolerabil- ity. It is widely available, inexpensive, and has an established safety profile. The trial investigating the efficacy of magnesium in stroke, the Intravenous Magnesium Efficacy Study (IMAGES), in which the patients treated within 12 hours of symptoms onset, showed no efficacy [16]. But IMAGE study was frayed by weaknesses that 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.06.001