Julien Bogousslavsky, MD; Bartlomiej Piechowski-Jozwiak, MD

Disclosures

September 07, 2004

Question

In my practice the use of magnesium in the early stages of a stroke has rendered the best results for my patients who have the greatest deficits. Why not recommend using magnesium as early as possible? What is the current status regarding the use of magnesium during both hemorrhagic and thrombotic strokes?

Al Pinto, MD

Response from Julien Bogousslavsky, MD and Bartlomiej Piechowski-Jozwiak, MD

Protecting the brain from ischemic damage remains a major target for stroke researchers. Lots of neuroprotective agents have been studied so far; however, none of them has been shown to be clearly efficacious for patients with stroke.

Some agents, including magnesium, have been used for other medical indications in humans, and have been shown to be devoid of serious adverse effects. But is magnesium an effective neuroprotectant in the setting of stroke?

Magnesium, an important cofactor in metabolism and protein synthesis, joins into a complex with adenosine triphosphate. Magnesium acts as a noncompetitive NMDA receptor blocker; it inhibits the release of excitatory neurotransmitters at the presynaptic level and blocks voltage-gated calcium channels. Moreover, it has been shown to suppress anoxic depolarization and cortical spreading depression -- both potential targets for neuroprotective treatment. Magnesium also exerts vascular effects, such as boosting vasodilatation, increasing the cardiac output, and prolonging bleeding time.

Magnesium homeostasis in the central nervous system is regulated by active transport, and its concentration in cerebrospinal fluid (CSF) is maintained at levels higher than serum levels. With intravenous administration, magnesium concentration in CSF can be increased with a peak at 4 hours. Magnesium is used in eclampsia to prevent seizures, and also is a very well-known antiarrhythmic agent. Its wide use reflects its safety and tolerability. Serious magnesium toxicity is marked by neuromuscular and cardiac conduction block. Most important, the effectiveness of magnesium in acute stroke has been demonstrated in animal studies.

A meta-analysis of 4 trials in which magnesium was administered to patients with acute stroke yielded an 8% absolute reduction in risk of death or dependence after 3-6 months from disease onset.[1] However, the combined cohort of patients included in this systematic review was small (less than 200 patients). The results of a small, randomized trial not included in this meta-analysis were more promising, with a trend toward a better functional outcome at 30 days in patients treated within 24 hours from onset vs controls.[2] The results of a large randomized trial, in which magnesium was administered intravenously less than 12 hours (median, 7 hours) from symptom onset were disappointing. Magnesium not only failed to show any beneficial effect on death and disability at 90 days, but it slightly increased mortality (odds ratio [OR], 1.21; 95% confidence interval [CI], 0.98-1.5). However, the investigators found a beneficial effect in a subgroup of patients with lacunar strokes (OR, 0.7; 95% CI, 0.53-0.92) and also in patients with a mean arterial blood pressure that was higher than the median (OR, 0.78; 95% CI, 0.61-0.99).[3] Intravenous magnesium sulfate administration during the hyperacute phase of stroke was shown to be safe in a small, open-label pilot trial, in which more than 70% of patients were treated less than 2 hours from symptoms onset. Dramatic early recovery was achieved in 42% of patients, and good functional outcome (modified Rankin scale ≤ 2) at 90 days post treatment was achieved by 69% of all patients and in 75% treated within 2 hours.[4]

The current state of knowledge does not allow for the practical use of magnesium in human stroke. Some data are promising, and require further evaluation in randomized, large-scale studies. According to the current European treatment guidelines, no neuroprotective treatment is recommended for stroke patients.[5]

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