Neuroprotection is a relatively newer approach in the management of stroke. The cardinal feature in the concept of neuroprotection was to boost tolerance to ischemic insult such that the tissue retains viability till other defence mechanisms come into play. Calcium ions play the sheet anchor role in the mechanism of cell injury by causing the release of excitatory amino acids like glutamate (through NMDA receptors), cell membrane lipid peroxidation, free radical generation and, ultimately, cell death.[8
] Magnesium is the second most common intracellular cation having a serum concentration of 1.72.6 mg/dL. It is believed to be nature's physiological calcium antagonist. The neuroprotective attributes of magnesium are presumed to be due to its (1) noncompetitive antagonism of NMDA receptors,[9
] (2) inhibition of glutamate release,[10
] (3) antagonism of all subtypes of calcium channels,[11
] (4) early restoration of cellular ATP reserves and (5) buffering of intramitochondrial calcium.[12
] The present study was undertaken to evaluate the effect of intravenous magnesium sulfate on the clinical outcome in patients of acute ischemic stroke.
Sixty patients of acute stroke presenting within 24 h were included as subjects in the study and were randomly divided into two equal groups of 30 each. Group 1 (magnesium group) and Group 2 (control group) were evenly matched for age and sex ratios. Subjects aged 60 years and above constituted the main bulk, an observation also reported by Park[13
] and Brodericks[14
] et al
. In the present study, hypertension emerged as the most common comorbid condition followed by hypercholesterolemia, ischemic heart disease and diabetes. The findings are consistent with the reports of previous authors. Saha and his associates observed in their study that 20% of the subjects were hypertensive while 8% had diabetes.[15
The dose of magnesium sulfate used was well tolerated as none of the subjects reported any adverse effects and they all remained hemodynamically stable during and after the magnesium therapy. On infusing magnesium, it was found that serum magnesium on Day 1 was more than double the value on Day 0 (t = 5.000 and P
< 0.001), and it remained elevated on Day 2 in comparison with serum magnesium levels on Day 0 (t = 5.000 and P
< 0.001) . On applying unpaired t-test to compare corresponding serum magnesium levels in the two groups, no significant difference was found between the magnesium levels on Day 0. However, a significant difference was observed on comparing the corresponding values on Day 1 (t = 5.000, P
< 0.001) and on Day 2 (t = 5.000, P
< 0.001) . This significant and sustained elevation in serum magnesium levels after magnesium infusion has also been reported by Wester et al
] and Muir et al
Many scoring systems have been proposed in the past for clinical evaluation in stroke patients. The Scandinavian scale was used for functional assessment (maximum 60 and minimum 0) in the present study due to its simplicity and practical value (annexure 1). A stroke score on the Scandinavian scale of 34.93 + 13.53, 44.27 + 11.48 and 50.03 + 9.87 was observed in the control group on Day 3, day of discharge and Day 28, respectively. On applying the paired t-test for mutual comparison (Day 3 vs. day of discharge, day of discharge vs. Day 28 and Day 28 vs. Day 3), the t-value was 5.000 (P < 0.001), 3.471 (P < 0.01) and 5.000 (P < 0.001), respectively .
In the magnesium group (Group 1), recovery scores observed on Day 3, day of discharge and Day 28 were 35.63 + 14.47, 45.47 + 13.30 and 50.43 + 11.02, respectively. On comparison of these values with paired t-test, the corresponding t-value for each pair was 5.000 and P <0.001 .
Unpaired t-test was applied to compare the corresponding stroke score (i.e., on Day 3, day of discharge and Day 28) in the two groups. The resultant t-values were 0.193, 0.374 and 0.149, respectively, demonstrating no significant correlation. Muir et al
. in a 3-month follow-up study found a similar response to magnesium therapy when compared with placebo.[17
] However, they found fewer early deaths in the magnesium group as compared with the placebo group. Survival curve analysis indicated slightly early recovery in the magnesium group (P
= 0.066 by long rank test). In a second study by Muir et al
] no significant difference in clinical outcome was seen with magnesium therapy. Lampl et al
] in their randomized, placebo-controlled, double-blind trial to study the protective effect of magnesium sulfate infusion reported at the end of 1-month follow-up that the Barthel index was nonsignificantly higher while the Rankin disability score was lower (marginally significant) in the magnesium group. They finally arrived at the conclusion that intravenous magnesium sulfate had a significant positive effect on the outcome in stroke patients, but further larger trials were needed to confirm this. Therefore, the marginal stroke recovery at 1-month follow-up was in accordance with the studies available in the literature.
But, Saver et al
] in a small pilot FAST-MAG trial demonstrated good functional outcome at 3 months after early administration of magnesium sulfate. The Intravenous Magnesium Efficacy in Stroke (IMAGES)[21
] trial recruited more than 2200 subjects within 12 h of stroke onset. The final results of the IMAGES trial demonstrated that randomised treatment with magnesium sulfate did not reduce the death and disability in stroke patients as compared with placebo. Further in-depth analysis of the IMAGES data by Aslanyan et al
] suggested a positive correlation between magnesium and lacunar syndrome, which was not ascribed to confounding factors like severity, time of treatment, blood pressure and other baseline factors. Moreover, the beneficial effect was found to be unrelated to the time from stroke onset to infusion of magnesium.
The present study failed to document a statistical significant stroke recovery in spite of achieving a significant rise in serum magnesium level, more than that necessary for neuroprotection with an intravenous magnesium sulfate regime. Therefore, in spite of the beneficial effects of magnesium therapy on the histological and functional outcome on cerebral ischemia in animal models, no beneficial effects on the functional outcome of stroke were accrued in man except in case of lacunar syndromes. Further clinical trials are necessary to determine the benefits, the dose, duration and timing of magnesium therapy for reducing the morbidity and mortality in lacunar syndromes.