Fever is an elevated body temperature triggered by the hypothalamus to support immune function, with normal axillary temperature in children ranging from 36.0°C to 37.7°C, and any values above this considered abnormal¹. 

The link between fever and epileptic seizures is well-established, with clinicians facing four distinct subgroups: children with febrile seizures, patients with controlled epilepsy where fever triggers new seizures, those with acute symptomatic seizures due to non-epileptic conditions, and patients with postictal fever. Distinguishing these cases, particularly in children with low-grade fever, can be challenging. According to the American Academy of Pediatrics, febrile seizures occur without intracranial infection, metabolic disturbances, or prior afebrile seizures, and are classified as simple or complex^2,3.Simple febrile seizures represent 65 to 90 percent of febrile seizures³ and require all of the following features: a duration of less than 15 minutes, generalized in nature, a single occurrence in a 24-hour period, and no previous neurologic problems². Febrile seizures (FS) are the single most common seizure type and occur in 2 to 5% of North American and European children younger than age 5 years with a peak incidence in the second year of life.  However, its occurrence is reportedly much high at 14% among Asian children.Risk factors for febrile seizures include developmental delay, viral infections, family history, certain vaccinations, and potentially iron and zinc deficiencies, with seizures more likely as temperature rises^4,5,6,7,8. Recent studies have also suggested that serum levels of elements like zinc, copper, magnesium, and calcium may be associated with febrile seizures in children⁹. Magnesium, the fourth most common cation in the body, plays a key role in cell membrane stability, nerve conduction, and inhibiting calcium’s effects on synaptic transmission. Hypomagnesaemia can lead to increased nerve and muscle excitability, and an inherited disorder of magnesium malabsorption has been linked to hypocalcaemia, tetany, and seizures in infants and older individuals..Low serum magnesium levels have been linked to central nervous system effects, including increased severity of epilepsy, with altered magnesium concentrations in both plasma and cerebrospinal fluid (CSF). However, studies on the role of serum magnesium in seizures, particularly febrile seizures in children¹⁰ have yielded inconclusive results, with some showing low levels and others reporting higher magnesium levels in epilepsy¹¹.

AIM

The aim of the present study was to establish serum magnesium levels in children with febrile convulsions

The study was conducted in collaboration between the Department of Pediatrics and the Department of Pathology at sardar patel medical college bikaner, as a case-control study from April 2023 to March 2024. The study focused on children aged 6 months to 6 years who were admitted to the hospital with fever, with or without seizures. Patient selection was based on specific inclusion and exclusion criteria. Children between the ages of 6 months to 5 years, who were developmentally normal and presented with febrile convulsions, were included in the study. Only children who experienced their first episode of febrile convulsion and were admitted to the hospital during the study period were considered for inclusion. The study excluded children with a history of congenital central nervous system anomalies, neonatal seizures, neuroinfections, or other metabolic conditions that could cause seizures. Additionally, children who had received magnesium supplements or those suffering from conditions such as diarrhea, protein-energy malnutrition, malabsorption syndrome, or other causes of hypomagnesemia or hypermagnesemia were excluded from the study.

Table 1: Group wise distribution of patients enrolled in the study

Out of a total of 100 patients enrolled in the study, a total of 50 (50%) were those who were having fever with convulsions and comprised the Case Group (Group I) of study. Remaining 50 (50%) patients were those who had fever without convulsions and comprised the Control Group (Group II) of study.

Graph1:Comparison of age of patients and gender of patients between two groups

The majority of patients were aged between 1 and 2 years (30% in both groups), with the least in the 4-5 year age range (10% in Group I and 8% in Group II). There was no significant age difference between the groups (p=0.986), and 68% of patients were male, resulting in a male-to-female ratio of 2.13:1.

Table 2: Comparison of patients between two groups for duration and type of fever

In both groups, over 70% of patients had a history of fever lasting less than one day, with no significant difference in fever duration (p=0.070) or type (p=0.317), though most had continuous fever, while a smaller percentage had intermittent fever.

Graph 2: Seizure Characteristics (Case Group only) (n=50)

Type                                                                                                     Duration

Frequency

Most convulsions were generalized tonic-clonic (92%), with 52% lasting 5-10 minutes; 92% had a single episode, and 90% had simple seizures, while 10% experienced complex seizures.

Table 3: Comparison of cause of fever between two groups

Upper respiratory infection (URI) was the most common cause of fever in both groups, followed by UTI, ADD, and viral infections, with no significant difference between groups in fever cause (p=0.787).

Table 4: Comparison of two groups according to family history of febrile seizures/Seizure Disorder

A family history of febrile seizures was significantly more common in Group I (20%) than in Group II (4%) (p=0.014), though there was no significant difference in family history of seizure disorder between the groups (p=0.558).                                                                            Table 5: Comparison of Body temperature

Body temperatures ranged from 98 to 103°F with no significant difference in patients with temperatures >100°F (p=0.300).

Table 6: Comparison of S. Magnesium levels between two groups

1. Magnesium levels were significantly lower in Group I (mean 1.75±0.48 mg/dl, with 42% <1.5 mg/dl) than in Group II (mean 2.04±0.26 mg/dl, all ≥1.6 mg/dl) (p<0.001).

Table 7: Comparison of two groups according to Mode of Management

All patients received paracetamol, with tepid sponging significantly more common in Group I (100% vs. 86%) and IV/rectal diazepam used in 16% of Group I; antibiotics were used in 22% of cases in both groups (p<0.05 for sponging and diazepam use).

Febrile seizures, affecting 2-5% of children aged six months to five years², can lead to long-term consequences like hippocampal injury and neurocognitive impairment, making it essential to study risk factors, including serum elements like zinc, copper, magnesium, and calcium, with magnesium deficiency linked to seizure disorders and cognitive protection⁹.           

This case-control study examined the correlation between serum magnesium levels and febrile convulsions in 100 children (6 months to 5 years), with 50 in the convulsions group (Group I) and 50 in the non-convulsions group (Group II); consistent with existing literature, 74% of cases were aged between six months and three years¹².

Both groups were matched for age, gender, duration, type, and cause of fever, with no significant differences observed, as cases and controls were intentionally matched for these clinical characteristics.

In present study, majority of children with febrile seizures were males (68%). Thus the male to female ratio was 2.13.  There is no clear-cut gender predilection for febrile seizure as reported in literature. Among the studies mentioning gender ratio as reviewed by us, Khosroshah et al. (2015)¹³ found it to be 0.76, thus indicating that there is wide variation in gender ratios in different studies and a skewed gender ratio as observed in present study might be just incidental or can be a gender-related bias in health-services utilization pattern.

In present study, more than three quarter (76%) of children in febrile convulsion group had a duration of fever <1 day and had continuous fever. In literature, as such no description regarding duration of fever / continuity of fever and febrile seizure episode has been reported.

With respect to predominance of upper respiratory tract infections our findings are in consonance with the observations of Sherlin and Ramu (2014)¹⁴ who also found the most common cause of fever in children with febrile convulsions to be upper respiratory tract infection. The high prevalence of respiratory tract infections as a cause of fever may be due to seasonal variations, which are common in India and contribute to the increased incidence of these infections.

In present study, significantly higher proportion of cases had a family history of febrile seizure (20%) as compared to controls (4%). Thus the present study endorses the observation that family history of febrile seizure is a risk factor for febrile seizure in children. However, the positive family history rate of FS in present study (20%) was relatively lower than that reported in literature (25-40%)^15,16,17. Family history of febrile seizures has been described to be the main risk factor for febrile seizure by some researchers¹⁸. Some of the workers have also found it to be a risk factor for recurrence too¹⁹. The relatively lower prevalence of positive family history in present study could be primarily attributed to a smaller sample size for this purpose.

Although the prevalence of fever >100°F was higher in the cases (42%) than controls (32%), this difference was not statistically significant, possibly due to the post-hoc nature of fever grading after the seizure and primary medication administration¹⁸.

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. In 1971, Chhaparwal et al.¹⁹ in their study also found that nearly one-half of the cases of febrile seizure had on admission magnesium levels lower than the average observed in normal children in the region.

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, Burhanoğlu et al. (1996)²⁰ using a study design that included patients with febrile convulsion, bacterial meningitis, viral CNS infection and control group did not find a significant difference in S. magnesium levels.

On the basis of above findings, it can be concluded that serum magnesium levels in children with febrile convulsions are generally of lower order as compared to that of children having fever but not having convulsions. Prevalence of magnesium deficiency is quite high (42%) in febrile convulsion patients thus indicating a possible link between magnesium deficiency and febrile seizures which probably also affects the complexity of seizures too.

1. de Siqueira LFM. Febrile Seizures: Update on Diagnosis and Management. Rev Assoc Med Bras. 2010;56(4):489-492. doi:10.1590/S0104-42302010000400029.
2. American Academy of Pediatrics Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281-1286. doi:10.1542/peds.2008-0939.
3. Waruiru C, Appleton R. Febrile seizures: an update. Arch Dis Child. 2004;89(8):751-756. doi:10.1136/adc.2003.028449.
4. Berg AT, Shinnar S, Shapiro ED, et al. Risk factors for a first febrile seizure: a matched case-control study. Epilepsia. 1995;36(4):334-341. doi:10.1111/j.1528-1157.1995.tb01004.x.
5. Bethune P, Gordon K, Dooley J, et al. Which child will have a febrile seizure? Am J Dis Child. 1993;147(1):35-39. doi:10.1001/archpedi.1993.02160250037011.
6. Ganesh R, Janakiraman L. Serum zinc levels in children with simple febrile seizure. Clin Pediatr (Phila). 2008;47(2):164-166. doi:10.1177/0009922807309406.
7. Hartfield DS, Tan J, Yager JY, et al. The association between iron deficiency and febrile seizures in childhood. Clin Pediatr (Phila). 2009;48(4):420-426. doi:10.1177/0009922808330775.
8. Vestergaard M, Hviid A, Madsen KM, et al. MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis. JAMA. 2004;292(3):351-357. doi:10.1001/jama.292.3.351.
9. Prasad R, Singh A, Das BK, et al. Cerebrospinal fluid and serum zinc, copper, magnesium and calcium levels in children with idiopathic seizure. J Clin Diagn Res. 2009;3:1841-1846.
10. Meret S, Henkin RI. Simultaneous direct estimation by atomic absorption spectrophotometry of copper and zinc in serum, urine and cerebrospinal fluid. Clin Chem. 1971;17:369-373. doi:10.1093/clinchem/17.4.369.
11. Alvarez Dominquez L, Prats-Quinzannos J, Calvetmieas E, et al. Study of calcium and magnesium in cerebrospinal fluid and its relation to different neurological diseases. Ann Esp Pediatr. 1978;11:753-762.
12. Donaldson D, Trotman H, Barton M, et al. Routine laboratory investigations in infants and children presenting with fever and seizures at the University Hospital of the West Indies. West Indian Med J. 2008;57(4):369-372. doi:10.7727/wimj.2008.057.
13. Khosroshah N, Ghadirian L, Kamrani K. Evaluation of magnesium levels in serum and cerebrospinal fluid of patients with febrile convulsion hospitalized in Bahrami Hospital in Tehran in 2010-2011. Acta Med Iran. 2015;53(12):778-781.
14. Swaminathan R. Magnesium metabolism and its disorders. Clin Biochem Rev. 2003;24(2):47-66.
15. Frantzen E, Lennox-Buchthal M, Nygaard A, et al. A genetic study of febrile convulsions. Neurology. 1970;20:909-917. doi:10.1212/WNL.20.9.909.
16. Annegers JF, Hauser WA, Elveback LR, et al. The risk of epilepsy following febrile convulsions. Neurology. 1979;29:297-303. doi:10.1212/WNL.29.3.297.
17. Hauser WA, Annegers JF, Anderson VE, et al. The risk of seizure disorders among relatives of children with febrile convulsions. Neurology. 1985;35:1268-1273. doi:10.1212/WNL.35.9.1268.
18. Berg AT, Shinnar S, Shapiro ED, et al. Risk factors for a first febrile seizure: a matched case-control study. Epilepsia. 1995;36(4):334-341. doi:10.1111/j.1528-1157.1995.tb01004.x.
19. Chhaparwal BC, Kohli G, Pottowali JN, et al. Magnesium levels in serum and in CSF in febrile convulsions in infants and children. Indian J Pediatr. 1971;38:241-245. doi:10.1007/BF02859341.
20. Burhanoğlu M, Tütüncüoğlu S, çoker C, et al. Hypozincaemia in febrile convulsion. Neuropediatrics. 1996;27(6):324-326. doi:10.1055/s-2007-973823.