A febrile seizure is a seizure occurring in children aged six months to five years with fever, without intracranial infection, metabolic disturbance, or a history of afebrile seizures^1,2. It is an age-dependent response of the immature brain to elevated body temperature, with potential predisposing factors such as family history, electrolyte disturbances, and genetic influences³.  Febrile seizures are strongly linked to fever, which is an adaptive mechanism involving the hypothalamus to stimulate the immune system⁴. Fever-related seizures can manifest as febrile seizures, fever-triggered seizures in epilepsy, acute symptomatic seizures, or postictal fever, with febrile seizures classified as simple or complex by the AAP⁵.The condition significantly impacts parents and caregivers, causing anxiety, stress, and repeated hospitalizations⁶. Febrile seizures, the most common seizure type in children under five, affect 2–5% of children in North America and Europe and up to 14% in Asia, peaking in the second year of life. Risk factors include developmental delays, neonatal complications, viral infections, family history, specific vaccinations, and deficiencies in iron, zinc, or magnesium^7,8. Magnesium, a vital intracellular cation, plays a key role in nerve conduction, membrane stability, and neuronal function, with its deficiency linked to increased excitability and seizures.Studies suggest that low serum magnesium levels may significantly impact the central nervous system, particularly in epilepsy, with a positive correlation between hypomagnesemia and epilepsy severity⁹. Severe epilepsy is often associated with lower plasma magnesium levels, while magnesium concentration in the cerebrospinal fluid (CSF) is found to be elevated, likely originating from CNS tissues¹⁰. These alterations in magnesium levels in plasma and CSF may result from functional impairments of cell membranes in epilepsy^11,12. Research exploring the role of serum magnesium in febrile seizures has produced mixed findings, with some studies reporting low magnesium levels and others showing elevated levels in epileptic conditions. Despite ongoing investigations, the relationship between magnesium levels and febrile seizures in children remains inconclusive. This highlights the need for further studies to clarify magnesium's role in seizure pathophysiology¹³.

AIM

To compare serum magnesium levels between patients of febrile convulsions and febrile children without convulsions.

This case-control study was conducted in the Department of Pediatrics in collaboration with the Department of Pathology sardar patel medical college bikanerat, from April 2023to March 2024. The study involved children aged 6 months to 6 years admitted to the facility with fever, with or without seizures. The sampling frame was defined by specific inclusion and exclusion criteria. For the cases, inclusion criteria included developmentally normal children aged 6 months to 5 years presenting with febrile convulsions admitted for the first time to the hospital. Exclusion criteria for cases included children with congenital CNS anomalies, neonatal seizures, neuroinfections, metabolic conditions causing seizures, or those who had received magnesium supplements. Additionally, children with conditions such as diarrhea, protein-energy malnutrition, malabsorption syndrome, or other causes of hypomagnesemia or hypermagnesemia were excluded. The control group comprised children who met the same criteria as the cases, except they did not have febrile convulsions

Table 1: Comparison of age of patients between two groups

Irrespective of the group, maximum number of patients were aged between 1 and 2 years (30% each) while minimum were aged 4-5 years (10% in Group I and 8% in Group II). In Group I, only 26% and in Group II, only 22% patients were aged above 3 years. Statistically, there was no significant difference between two groups with respect to age (p=0.986).

Table 2: Comparison of Body temperature between two groups

Body temperature ranged from 98 to 103oF. Mean body temperature of patients in Group I was 100.22±1.35 as compared to 100.08±0.86oF in Group II. Though the proportion of patients with body temperature >100oF was higher in Group I (42%) as compared to that in Group II (32%) yet this difference was not significant statistically (p=0.300).

Table 3: Comparison of hematological parameters between two groups

Statistically, no significant difference was observed between two groups with respect to mean haemoglobin, neutrophil, lymphocyte and monocyte levels, however, mean TLC levels were found to be significantly higher in Group I (9.35±2.73 x 103) as compared to that in Group II (8.13±2.45 x 103) (p=0.021) whereas mean eosinophil level was higher in Group II (3.56±1.13%) as compared to that in Group I (2.66±0.94%) (p<0.001).

Table 4: Comparison of S. Magnesium levels between two groups

In Group I, S. Magnesium levels ranged from 0.9 to 2.5 mg/dl. A total of 21 (42%) patients had S. Magnesium levels <1.5 mg/dl and remaining 29 (58%) had S. Magnesium levels in range 1.6-2.5 mg/dl. Mean S. magnesium level in Group I was 1.75±0.48 mg/dl.In Group II, S. Magnesium levels ranged from 1.6 to 2.5 mg/dl. Thus, all had S. Magnesium levels in range 1.6-2.5 mg/dl. Mean S. magnesium level in Group II was 2.04±0.26 mg/dl.Statistically, there was a significant difference between two groups for both parametric as well as categorical comparisons (p<0.001).

Table 5: Association of S. Magnesium levels with different clinical characteristics

Statistically, no significant association of S. Mg levels could be seen with duration and type of fever, convulsion type, duration of seizure and number of seizure episodes. Mean S. Mg level was found to be significantly higher in cases having complex seizures as compared to those having simple seizures (p=0.046).

The distribution of age groups shows the highest representation in the 1-2 years category (30%) for both Group I and Group II, followed by the 2-3 years category (24%). The <1 year group also has notable representation, with Group II showing a slightly higher proportion (24%) compared to Group I (20%).

Prevalence of those having fever >100oF was higher in cases (42%) as compared to controls (32%), however, this difference was not significant statistically. Although febrile seizure by definition is a seizure accompanied by fever (temperature >100.4oF or 38oC by any method)¹⁴, however, this discrepancy might be attributed to the fact that the grade of fever recorded in present study was post-hoc in nature, i.e., at a time when febrile seizure had already occurred and most of the patients had taken primary medication by the time this evaluation was done. Being a tertiary care centre, it was not possible for us to record the exact fever grade at the time of seizure and to verify the proposition that fever grade might be associated with higher odds of a first febrile seizure¹⁵.

On hematological assessment, a significant difference between cases and controls was observed with respect to TLC levels which were significantly higher in cases as compared to controls and eosinophil levels which were significantly higher in controls as compared to cases. Although increased leukocyte count is often indicated as a marker for infection, however, Donaldson et al. (2008)¹⁶ in their study also found leukocytosis in 35% cases amongst children presenting with fever and seizures and did not found it to be associated with meningitis or an underlying bacterial infection.  The findings of present study also indicate a similar trend. On the other hand, the higher eosinophil level in controls could be attributed probably to the presence of parasites/infection.

 In present study, mean S. magnesium levels of cases were significantly lower as compared to that of controls. With respect to S. magnesium levels <1.5 mg/dl, a total of 42% of cases as compared to none of the controls had S. magnesium levels below this cut-off. Thus this cut-off value was seen to be 42% sensitive and 100% specific for febrile seizures. Attempts to find out association of magnesium levels with an increased risk of febrile seizure are quite old. Similar observations were also made by some other workers too¹⁷.

In present study, although we did not have normal children yet among children having fever without febrile seizure, the average value was much higher than that of the children having febrile seizure, thus indicating that low S. magnesium levels have a detrimental impact on the CNS which might have resulted in febrile seizure. Contrary to our findings, Rutter and Smales (1976)¹⁸ did not find a significant difference in blood magnesium levels of cases as compared to that of normal children. In seizure, encephalitis and fever with meningismus found a mean magnesium levels in CSF to be significantly lower as compared to the other two groups despite having a group sizes ranging from 20 to 26 patients.

In present study, we had a relatively larger sample size for both the groups, however, even in that situation, despite finding a significant association of S. magnesium levels with febrile seizures, it was found to be only 42% sensitive but 100% specific. Similar to our study, Derakshan et al. (2010)¹⁹ using same cut-off level for S. magnesium found it to be only 25% sensitive but 100% specific. 

With respect to mean serum Mg levels in cases and controls, our findings are close to the observations made by Khas et al. (2014)²⁰ who reported mean levels of magnesium were 1.96±0.28 mg/dl and 2.15±0.24mg/dl in cases with FC and febrile patients without seizure. These results are quite close to our observations where mean S. magnesium levels of cases were 1.75±0.48 mg/dl as compared to 2.04±0.26 mg/dl for controls.

In present study we also studied association of S. magnesium levels with duration of fever, type of fever, convulsion type, duration, number of episodes and complexity, however, we could found this association to be significant only for complexity with mean S. magnesium levels of patients with simple seizures to be significantly lower as compared to that of patients with complex seizures. This is a new relationship found in present study and as such no previous study has found such relationship. In view of limited number of cases with complex seizures (n=5) in present study, this relationship warrants further exploration.

The findings in present study and their analysis in light of empirical evidence available, shows that magnesium deficiency might be instrumental in triggering febrile seizure, however, given its low sensitivity yet high specificity, its definitive association in all the cases cannot be established. The findings thus suggest that although magnesium deficiency plays an important role in triggering febrile seizures yet it should not be viewed as the only marker. Given the complex pathophysiology involved with a rather unclear role of magnesium, this issue should be explored further.

The study highlights that magnesium deficiency may play a significant role in triggering febrile seizures, supported by significantly lower serum magnesium levels in cases compared to controls. While S. magnesium <1.5 mg/dL showed 100% specificity for febrile seizures, its sensitivity was limited to 42%, indicating it is not the sole marker. The study also found an association between serum magnesium levels and seizure complexity, which requires further exploration. Elevated TLC levels in cases and eosinophil levels in controls suggest distinct hematological trends. Further research is needed to clarify the role of magnesium in febrile seizures and its potential as a diagnostic marker.

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