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|Year : 2022 | Volume
| Issue : 5 | Page : 1852-1855
Serum Magnesium Levels During the Ictal and Interictal Phase in Patients of Migraine: A Prospective Observational Study
Rahul Mahajan1, Kuljeet Singh Anand1, Rakesh Kumar Mahajan2, Jyoti Garg1, Abhishek Juneja1
1 Department of Neurology, ABVIMS and Dr. RML Hospital, New Delhi, India
2 Department of Microbiology, ABVIMS and Dr. RML Hospital, New Delhi, India
|Date of Submission||05-May-2020|
|Date of Decision||20-Aug-2020|
|Date of Acceptance||03-Oct-2020|
|Date of Web Publication||21-Oct-2022|
Department of Neurology, ABVIMS and Dr. RML Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Migraine is one of the primary headaches having a global prevalence of 15%. It is characterized by neurovascular dysfunction and recurrent episodes of headache. The hyperexcitability of the cerebral cortex has been recognized as an important factor in the pathogenesis of migraine, and magnesium (Mg) being a regulator of neuronal excitability is thought to participate in migraine pathogenesis.
Objectives: To determine the serum levels of Mg in patients of migraine during the attack and in between attacks as compared to healthy controls.
Methods: A total of 50 patients of migraine who fulfilled inclusion criteria were enrolled in the study along with the same number of healthy controls. International Classification of Headache Disorders 3rd Edition, 2013 (ICHD-III) criteria was used for the diagnosis of migraine.
Results: The mean serum Mg in migraine cases during the interictal phase was lower than healthy controls (1.849 ± 0.135 vs 2.090 ± 0.205, P < 0.001), which was statistically significant. It was also found that mean serum Mg during attacks was significantly lower than in between attacks (1.822 ± 0.149 vs 1.849 ± 0.135, P = 0.003). Serum Mg levels in migraine cases showed an inverse linear relationship with the frequency of attacks.
Conclusion: Relatively low serum Mg in migraine cases when compared with healthy controls and inverse relation of serum Mg levels with the frequency of migraine attacks suggests that Mg is significantly involved in mechanisms underlying migraine pathogenesis, which can be explored as a therapeutic option.
Keywords: Magnesium, migraine, neurovascular, pathogenesis
Key Message: Magnesium plays a significant role in migraine pathogenesis. Establishing a correlation between serum magnesium levels and susceptibility to migrainous attacks will help in the exploration of magnesium as antimigraine therapy.
|How to cite this article:|
Mahajan R, Anand KS, Mahajan RK, Garg J, Juneja A. Serum Magnesium Levels During the Ictal and Interictal Phase in Patients of Migraine: A Prospective Observational Study. Neurol India 2022;70:1852-5
|How to cite this URL:|
Mahajan R, Anand KS, Mahajan RK, Garg J, Juneja A. Serum Magnesium Levels During the Ictal and Interictal Phase in Patients of Migraine: A Prospective Observational Study. Neurol India [serial online] 2022 [cited 2023 Dec 10];70:1852-5. Available from: https://www.neurologyindia.com/text.asp?2022/70/5/1852/359247
Migraine is one of the primary headaches, which is considered to be a neurovascular disorder. It is known to mankind since ancient times as evidenced by Hippocrates (c.460-c. 370 BC) descriptions of recurrent episodes of headache with migrainous features. With an estimated global prevalence of 15%, it leads to an enormous loss of productive life years., The hyperexcitability of the cerebral cortex has been recognized as an important factor in the pathogenesis of migraine which leads to a cascade of cortical spreading depression, vascular dysfunction, and sterile neurogenic inflammation., There is a continuous quest for the search of physiological forces that have either direct or indirect involvement in the described mechanisms of pathophysiology of migraine so that new targets for antimigraine therapies could be identified since the existing therapies have proven to be insufficient in a substantial proportion of migraine patients. Magnesium (Mg) concentration affects N-Methyl D-Aspartate (NMDA) receptors, serotonin receptors, and other migraine-related receptors and neurotransmitters, thereby regulating neuronal excitability. Due to these effects, Mg has attracted attention regarding its role in the pathophysiology of migraine and as a potential therapeutic agent. There have been few studies in India that have explored the relationship of migraine with serum levels of Mg. This study aimed to determine the serum Mg levels in patients of migraine during the attack and in between attacks as compared to healthy controls.
| » Materials and Methods|| |
This was a prospective observational study to evaluate the serum levels of Mg in patients of migraine during the attack and in between attacks as compared to healthy controls. Institutional Ethics Committee approved the study on 22-12-2017. A total of 50 patients of migraine who fulfilled inclusion criteria were enrolled in the study. International Classification of Headache Disorders 3rd Edition, 2013(ICHD-III) criteria was used for the diagnosis of migraine. Healthy controls were enrolled from hospital staff, attendants of patients, and the general population. Written informed consent was taken from all the cases and controls before inclusion in the study.
(a) Adult males and females in the age group of 18–45 years were diagnosed based on ICHD-III criteria as migraine cases. (b) Age (±2 years), sex-matched healthy controls with comparable body mass index (BMI).
Patients having (a) nonmigrainous headache (b) chronic migraine (headache ≥15 days/month) (c) on prophylactic therapy for migraine (d) known cases of diabetes mellitus, arterial hypertension, dyslipidemia, head injury, chronic renal disease, gastrointestinal diseases like malabsorption syndrome and antacid abuse, thyroid disorders, hyper/hypoparathyroidism (e) history of epilepsy or stroke and cardiovascular disease (f) BMI <18 kg/m2 or >35 kg/m2 (g) any substance abuse and nicotine dependence (h) pregnancy or lactation (i) drug use such as hormonal drugs, calcium, and Mg supplements within last 3 months, diuretics, aminoglycosides, acetazolamide, and amphotericin B.
History of migraine was elicited in detail from migraine cases regarding the age of onset, duration of disease, migrainous attacks per month, and the average duration of headache attacks. Headache characteristics like triggering factors, aura and its type, location, nature, severity, onset to peak latency, and accompanying symptoms were noted. Visual analog scale score (range, 1 [minimum pain] to 100 [maximum pain]) was used to assess the severity of pain during migraine attacks. After obtaining other relevant history regarding any comorbidities and smoking habits, study participants that include both migraine cases and healthy controls underwent general, physical, and neurological examination. Blood samples of migraineurs were taken in the morning after fasting for a minimum of 8 h, once during their headache attack (or within 24 h after headache) and then at least 7 days after their last migrainous headache (interictal phase). Blood samples of controls were taken in the morning after a minimum of 8 h of the fasting period. Estimation of serum Mg levels was done in the biochemistry laboratory, by a colorimetric test using slides manufactured by Vitros Chemistry Products.
Data collected had categorical variables (numbers and percentages) and continuous variables (mean ± SD and median). Kolmogorov-Smirnov test was used to test the normality of data. Unpaired t-test/Mann-Whitney U test was used to compare quantitative variables between the two groups while the paired t-test/Wilcoxon test was used to compare quantitative variables during the ictal and interictal phase. Chi-square test/Fisher's exact test was used for comparison of qualitative data. The P value of < 0.05 was kept statistically significant. The data were analyzed using MS EXCEL spreadsheet and statistical package for social sciences (SPSS) version 21.0.
| » Results|| |
There was no significant difference regarding age, sex, and BMI distribution in the migraine and control group as depicted in [Table l]. The majority of study participants (68%) were females belonging to the age group of <30 years having normal BMI. Among migraine cases, 34 out of 50 did not have any aura, most of them had a disease duration of less than 5 years as depicted in [Table 2]. The mean serum Mg levels in migraine cases were lower than healthy controls during the interictal phase (1.849 ± 0.135 vs 2.090 ± 0.205, P < 0.001), which was significant. It was also observed that mean serum Mg levels during headache attacks were lower than in the interictal phase (1.822 ± 0.149 vs 1.849 ± 0.135, P = 0.003) as depicted in [Figure 1]. There was no significant difference in serum levels of Mg with age, sex, BMI, duration of disease, and the presence or absence of aura, but mean serum Mg levels in migraine cases with frequency ≥4/month was significantly lower than migraine cases with frequency <4/month (P < 0.001) as shown in [Table 3]. There was a negative linear relationship between serum Mg and frequency of attacks in migraine cases as shown in [Figure 2].
|Table 1: General characteristics of the migraine cases and healthy controls|
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|Table 2: Distribution of migraine cases according to disease duration, frequency of attacks, presence of aura, pain severity, and associated symptoms|
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|Table 3: Relation of serum magnesium (mg) with various factors in migraine cases and controls|
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| » Discussion|| |
The present study showed mean serum Mg levels in migraine cases during the interictal phase were lower than in the healthy controls (P < 0.001). Also among migraine patients, the levels of serum Mg were significantly lower during the attack phase than during the interictal phase. Mg being a regulator of excitability of neurons, plays an important role in the pathogenesis of migrainous headaches. Mg concentration through its effect on many of migraine-associated neurotransmitters and receptors is involved in many pathophysiologic mechanisms including cortical spreading depression, central sensitization, and trigeminovascular pathway activation. Many previous studies have shown lower serum Mg concentrations in the interictal periods of migraineurs when compared to healthy young individuals.,, There is a paucity of literature regarding the change in serum Mg levels during migraine attacks from the interictal phase. Ramadan et al. found that brain Mg (measured with 31-Phosphorus Nuclear Magnetic Resonance Spectroscopy) in migraine patients during the migrainous attack was on the lower side when compared to healthy controls. Sarchielli et al. also reported similar findings in his study that there was a decrease in the mean serum Mg levels of migraine cases during the attack period as compared to the interictal period. In contrast Samaie et al. found that there was no difference in the serum Mg levels during migraine attacks and interictal phase. Mauskop et al. reported a high incidence of Mg deficiency during menstrual migraines providing evidence that Mg deficiency has a role in the pathogenesis of menstrual migraines. It was suggested that hormonal actions on Mg may be the reason for the menstrual migraine genesis and intravenous administration of Mg may help in terminating menstrual migrainous attacks. Similar mechanisms involving Mg metabolism may be implicated in the precipitation of non-menstrual migraine attacks by triggers such as stress, sleep deprivation, and fasting. The mean serum Mg levels in migraine cases with frequency ≥4/month was significantly lower than migraine cases with frequency <4/month (P < 0.001), thus raising the possibility that serum Mg may have a role in defining susceptibility of individuals to migrainous headaches and threshold of migraine attacks because of its implication in various mechanisms of migraine pathogenesis. Some past studies have also reported an inverse correlation of serum Mg levels with the frequency of migraine attacks., Pharmacological approaches that are available today for migraines are effective in only a limited number of patients and there is a need for better approaches. The role of Mg in defining the threshold for migraine attacks and its involvement in the pathophysiologic mechanisms of migraine has become evident recently which makes it a potential therapeutic agent in migraine. Our study had the limitation of measuring total serum Mg rather than the ionized form which has actual biological effects. Although various mechanisms have been suggested to explain the association between Mg and the physiologic threshold for migraine, more studies at cellular and molecular levels are needed to further validate this association and explore the potential of Mg as a treatment of migraine.
| » Conclusion|| |
Relatively low serum Mg in migraine cases when compared with healthy controls and inverse relation of serum Mg levels with the frequency of migraine attacks suggests that Mg is significantly involved in mechanisms underlying migraine pathogenesis, which can be explored as a therapeutic option.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]