Magnesium Sulfate in the Management of Acute Ischemic Stroke: A Review of the Literature and Future Directions

The management of acute ischemic stroke (AIS) was revolutionized within the last 15 years with the introduction of mechanical thrombectomy (MT) to standard of care. Despite the success of mechanical thrombectomy (MT) in achieving high recanalization rates for large vessel occlusion, functional independence post-treatment remains suboptimal. The current limitations of MT prompt evaluation of the role of adjunctive pharmacologic neuroprotective therapies to prevent excitotoxicity, cellular apoptosis, and inflammation that cause irreversible neuronal damage during AIS. Magnesium (MgSO4) provides an attractive neuroprotectant profile, having many different effects, and is inexpensive, readily available, and has a long-established safety and tolerability profile in the management of myocardial infarction and eclampsia. This gap between technical success and patient outcomes is largely due to the inability to fully protect brain tissue from infarction during ischemia. MgSO4 has shown promise in preclinical studies for its neuroprotective properties, including blocking NMDA receptors, increasing cerebral blood flow, and stabilizing ion channels. However, clinical trials, such as FAST-MAG and IMAGES, failed to demonstrate significant benefits when MgSO4 was administered intravenously, due to delayed drug administration or delivery to target tissue. These trials highlighted the need for faster, more targeted drug delivery. Intra-arterial (IA) administration of MgSO4 via the catheter used in MT could address these limitations by delivering high doses directly to ischemic brain tissue, potentially enhancing neuroprotection while reducing systemic exposure. Preclinical studies and some clinical trials have demonstrated the safety and feasibility of IA, but not IA MgSO4. Further investigation is needed to assess its efficacy. While past trials have not succeeded, IA administration of neuroprotective agents like MgSO4 may improve functional outcomes in stroke patients post-MT. Ongoing and future studies will determine if this approach can effectively complement reperfusion strategies, potentially ushering in a new era of stroke care.