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Magnesium as an Effective Adjunct Therapy for Drug Resistant Seizures

Published online by Cambridge University Press:  02 December 2014

Peter A. Abdelmalik
Affiliation:
Division of Fundamental Neurobiology, Toronto Western Research Institute
Nina Politzer
Affiliation:
Division of Neurology, Toronto Western Hospital
Peter L. Carlen*
Affiliation:
Division of Fundamental Neurobiology, Toronto Western Research Institute Division of Neurology, Toronto Western Hospital Department of Medicine (Neurology) and Physiology, University of Toronto, Toronto, Ontario, Canada
*
Toronto Western Hospital, 5W-442, 399 Bathurst St., Toronto, Ontario, M5T2S8, Canada.
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Abstract

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Objective:

To explore the use of magnesium (Mg), an endogenous ion and enzymatic co-factor used in a variety of medical applications, for the treatment of epileptic seizures resistant to traditional medical therapy.

Background:

For almost a century, Mg has been used as prophylaxis and treatment of seizures associated with eclampsia. Mg is a CNS depressant, with numerous functions intracellularly and extracellularly. However, because of the availability of well studied anticonvulsant drugs, Mg has not been tested widely in the treatment of epileptic seizures.

Methods:

A retrospective chart review of 22 cases of drug resistant epilepsy, where a trial of empiric oral Mg supplementation (mainly in the form of Mg-oxide) was conducted.

Results:

Oral Mg supplementation was associated with a significant decrease in the number of seizure days per month, from 15.3 ± 13.2 (mean ± SD) to 10.2 ± 12.6 at first follow up (3-6 months, p=0.021), and to 7.8 ± 10.0 seizure days/month at second follow up (6-12 months, p=0.004). Thirty-six percent had a response rate of 75% or greater at second follow-up. Two patients reported seizure freedom. Most patients were well maintained on MgO 420mg twice a day, or in 2 cases, Mg Lactate, without significant adverse effects, the most frequent being diarrhea (4/22).

Discussion:

These results suggest that oral Mg supplementation may prove to be a worthwhile adjunctive medication in treating drug intractable epilepsy.

Conclusions:

A prospective, double-blinded, placebo controlled study is warranted to evaluate the potential of Mg for the treatment of drug-resistant seizures.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2012

References

1Lazard, EM.A preliminary report on the intravenous use of magnesium sulfate in puerperal eclampsia. Am J Obstet Gynecol. 1925;9:17888.Google Scholar
2Duley, L, Henderson-Smart, DJ, Walker, GJ, Chou, D.Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev. 2010;8(12):CD000127.Google Scholar
3Duley, L, Henderson-Smart, DJ, Chou, D.Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database of Syst Rev. 2010;6(10):CD000128.Google Scholar
4Goldman, RS, Finkbeiner, SM.Therapeutic use of magnesium sulfate in selected cases of cerebral ischemia and seizure. N Engl J Med. 1988;319(18):12245.Google Scholar
5Sen, A, Gulati, A.Use of magnesium in traumatic brain injury. Neurotherapeutics. 2010;7(1):919.Google Scholar
6Muir, KW, Lees, KR, Ford, I, Davis, S, Investigators. IMEiSIS. Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet. 2004;363 (9407):43945.Google Scholar
7Zou, L-P, Wang, X, Dong, C-H, Chen, C-H, Zhao, W, Zhao, R-Y.Three-week combination treatment with ACTH + magnesium sulfate versus ACTH monotherapy for infantile spasms: A 24-week, randomized, open-label, follow-up study in China. Clin Ther. 2010;32(4):692700.Google Scholar
8Kanbay, M, Goldsmith, D, Uyar, ME, Turgut, F, Covic, A.Magnesium in Chronic Kidney Disease: Challenges and Opportunities. Blood Purif. 2010;29(3):28092.Google Scholar
9Elin, RJ.Magnesium metabolism in health and disease. Dis Mon. 1988;34(4):161218.Google Scholar
10Sinert, R, Zehtabchi, S, Desai, S, Peacock, P, Altura, BT, Altura, BM.Serum ionized magnesium and calcium levels in adult patients with seizures. Scand J Clin Lab Invest. 2007;67(3):31726.Google Scholar
11Aali, BS, Khazaeli, P, Ghasemi, F.Ionized and total magnesium concentration in patients with severe preeclampsia-eclampsia undergoing magnesium sulfate therapy. J Obstet Gynaecol Res. 2007;33(2):13843.Google Scholar
12Mody, I, Lambert, JD, Heinemann, U.Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J Neurophysiol. 1987 Mar;57(3):86988.Google Scholar
13Krauss, GL, Kaplan, P, Fisher, RS.Parenteral magnesium sulfate fails to control electroshock and pentylenetetrazol seizures in mice. Epilepsy Res. 1989;4(3):2016.CrossRefGoogle ScholarPubMed
14Mikati, MA, Injibar, H, Kurdi, RM, et al.Effects of magnesium sulfate in kainic acid-induced status epilepticus. J Med Liban. 2006;54(4):2004.Google Scholar
15Standley, CA, Irtenkauf, SM, Cotton, DB.Anticonvulsant Effects of Magnesium Sulfate in Hippocampal-Kindled Rats. J Biomed Sci. 1995;2(1):5762.Google Scholar
16Cotton, DB, Hallak, M, Janusz, C, Irtenkauf, SM, Berman, RF.Central anticonvulsant effects of magnesium sulfate on N-methyl-Daspartate-induced seizures. Am J Obstet Gynecol. 1993;168(3 Pt 1):9748.Google Scholar
17Safar, MM, Abdallah, DM, Arafa, NM, Abdel-Aziz, MT.Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats. Brain Res. 2010; 1334:5864.Google Scholar
18Borges, LF, Gücer, G.Effect of magnesium on epileptic foci. Epilepsia. 1978;19(1):8191.Google Scholar
19Sibai, BM, Spinnato, JA, Watson, DL, Lewis, JA, Anderson, GD.Effect of magnesium sulfate on electroencephalographic findings in preeclampsia-eclampsia. Obstet Gynecol. 1984;64 (2):2616.Google Scholar
20Koontz, WL, Reid, KH.Effect of parenteral magnesium sulfate on penicillin-induced seizure foci in anesthetized cats. Am J Obstet Gynecol. 1985;153(1):969.Google Scholar
21Temkin, NR, Anderson, GD, Winn, HR, et al.Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Lancet Neurol. 2007;6(1):2938.Google Scholar
22Sadeh, M, Blatt, I, Martonovits, G, Karni, A, Goldhammer, Y.Treatment of porphyric convulsions with magnesium sulfate. Epilepsia. 1991;32(5):7125.Google Scholar
23Visser, N, Braun, K, Leijten, F, van Nieuwenhuizen, O, Wokke, J, van den Bergh, W.Magnesium treatment for patients with refractory status epilepticus due to POLG1-mutations. J Neurol. 2011;258 (2):21822.Google Scholar
24Firoz, M, Graber, M.Bioavailability of US commercial magnesium preparations. Magnes Res. 2001;14(4):25762.Google Scholar
25Coudray, C, Rambeau, M, Feillet-Coudray, C, et al.Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res. 2005;18(4):21523.Google Scholar
26Oppelt, WW, MacIntyre, I, Rall, DP.Magnesium exchange between blood and cerebrospinal fluid. Am J Physiol. 1963;205(5): 95962.Google Scholar
27Sun, L, Kosugi, Y, Kawakami, E, Piao, YS, Hashimoto, T, Oyanagi, K.Magnesium concentration in the cerebrospinal fluid of mice and its response to changes in serum magnesium concentration. Magnes Res. 2009;22(4):26672.Google Scholar
28Thurnau, GR, Kemp, DB, Jarvis, A.Cerebrospinal fluid levels of magnesium in patients with preeclampsia after treatment with intravenous magnesium sulfate: a preliminary report. Am J Obstet Gynecol. 1987;157(6):14358.CrossRefGoogle ScholarPubMed
29McKee, J, Brewer, R, Macy, G, Borel, C, Reynolds, J, Warner, D.Magnesium neuroprotection is limited in humans with acute brain injury. Neurocrit Care. 2005;2(3):34251.Google Scholar
30Fuchs-Buder, T, Tramèr, MR, Tassonyi, E.Cerebrospinal Fluid Passage of Intravenous Magnesium Sulfate in Neurosurgical Patients. J Neurosurg Anesthesiol. 1997;9(4):3248.Google Scholar
31Hallak, M, Berman, RF, Irtenkauf, SM, Evans, MI, Cotton, DB.Peripheral magnesium sulfate enters the brain and increases the threshold for hippocampal seizures in rats. Am J Obstet Gynecol. 1992;167(6):160510.Google Scholar