Abstract
Objective
Febrile seizure (FS) is one of the most common neurological problems during childhood.Pathogenesis of febrile convulsion is unknown. This study investigated some trace elements among children admitted with FS compared with thoseof febrile without seizure attacks.
Materials & Methods
This case-control study was conducted on48 children (6 months to 5 yrold) diagnosed with febrile seizure as the cases and 48 age-matched febrile children as the control group. Serum levels of magnesium, calcium, sodium, potassium, and serum zinc were measured. Statistical analysis was performed with SPSS (version 15) using Student t-test.
Results
There were no significant differences between the cases and controls in terms of gender or age. The means of serum level of zinc, sodium, calcium and magnesium in the case group was lower than those of the control group. There was no significant difference onserum potassium mean level between the case and control groups.
Conclusion
Deficiency of trace elements was correlated significantly with febrile convulsion, while further investigations on trace elements are required.
Key Words: Zinc, Sodium, Calcium, Magnesium, Febrile convulsion, Children
Introduction
Febrile seizure (FS) is a highly common neurological problem at childhood (1). Approximately, 2%-5% of children are estimated to undergo at least one seizure during a febrile illness before they get 5 yrold (2), accounting for 30% of all seizures among children. Seizure is associated with feveralthough there is no evidence of intracranial infection or a definite cause for it (1, 2). The mechanisms underlying FS have multifactorial etiology, complicated by the fact that the pathogenesis of FS is unknown in most cases. FS represents the point between a low seizure threshold and genetic components. Several essential elements play important roles in redox reactions, in connective tissue or cell membranes, in stabilization of biological molecules, and in control of biological processes by facilitating the binding of molecules to receptor sites on cell membranes (3). While disturbance in serum electrolytes is considered as a pathogenetic theory of FS, it has not been confirmed as yet. Low levels of someelements such as iron and sodium (Na) in the blood play roles in repeated occurrence of FS (4). We aimed to investigate some trace elements among children admitted with FS compared with thoseof febrile without seizure attacks.
Materials & Methods This case-control study, conducted in a hospital in eastern Iran, enrolled96 individuals including 48 children aged6 months to 5 yrdiagnosed with febrile convulsion (FC) as the case group, and 48 age-matched children with fever but without seizure as the controls who were from the same setting. Inclusion criteria for the cases were patient with fever (≥ 38 ºC) and a history of seizure within the last 6 h, normal cerebrosspinal fluid examination,no metabolic disorder, no intake of serum, and no pneumonia, gastroenteritis, kidney, cardiac, or developmental disorder. The control group had the same criteria except for seizure. On the other hand, the patients who had no evidence of central nervous system infection, epilepsy, metabolic seizures, or those who were already on zinc therapy or other elements for any other ailment such as malnutrition, diarrhea, pneumonia or acrodermatitisenteropathica were excluded. Blood samples (5 ml) were taken on the first hours of admission for zinc (Zn), magnesium (Mg), calcium (Ca), sodium (Na) and potassium (K). Serum levels of Mg, Ca, Na, and K were measured usinga photometric method using an auto analyzer device, and serum Zn was measured by atomic absorption spectrophotometry. The exact goal of the project was explained to the parents of the children and informed consents were taken from them. Local Ethics Committee confirmed the process. Statistical analysis was performed usingSPSS version 15 (Chicago, IL, USA) using Student t-test. Data were expressed as the mean ± standard deviation (SD). The significant level was set for P<0.05.
Results
There were no significant differences between the cases and controls with regard to gender (P=0.64) or temperature (P=0.084) (Table 1). The mean age of FS cases was 24.1±13.4 months and that of the controlgroup without FS was 19.8±11.1 months, indicating a statistically insignificant difference (P=0.09). Besides, serum mean levels of zinc, Na, Ca and Mg in the case group were lower than those of the control group (Table 2). There was no significant difference in the serum mean K level between the case and control groups (4.38±0.41 and 4.5±0.51 respectively) (Table 2).
Table 1.
Comparison between Cases and Controls regarding Age and Gender
| Group | Cases (n=48) | Controls (n=48) | P -value |
|---|---|---|---|
| variable | |||
| Age (months) | 24.1±13.4 | 19.8±11.1 | P=0.09 |
| Sex | |||
|
Male
Female |
18 (37.5%) 30 (62.5%) |
20 (41.7%) 28 (58.3%) |
P=0.68 |
Table 2.
Comparison between Cases and Controls regarding Laboratory Data
| Group | Cases (n=48) | Controls (n=48) | Independent t -test |
|---|---|---|---|
| Variable | |||
| Na | 136.2±3.3 | 140±3.9 | P<0.001 |
| K | 4.38±0.41 | 4.5±0.51 | P<0.22 |
| Ca | 8.79±0.47 | 9.17±0.59 | P<0.001 |
| Zn | 80.5±21.7 | 117.2±35.5 | P<0.001 |
| Mg | 1.9±0.32 | 2.27±0.38 | P<0.001 |
Discussion
FS is the most common cause of seizures among children. It has been known since ancient times that seizures frequently accompany fever in young children. The exact pathogenesis is unknown but involves factors such as genetic predisposition and alterations. In the present study, we investigated the levels of trace and major element concentrations among children with FS. Ourresults showed that bio-element levels were affected in children with FS. The changes in bioelements in FS explained the response of the metabolism. Zinc is a component of more than 300 different enzymes that functions in many aspects of cellular metabolism, involving metabolism of proteins, lipids, and carbohydrates (5). It is believed that Zn as a co-factor of glutamic acid decarboxylase modulates the production of gammaaminobutyric acid in the central nervous system. It modulates the activity of glutamic acid decarboxylase, which is a rate limiting enzyme in the synthesis of gammaaminobutyric acid (GABA). Furthermore, it increases the affinity of neurotransmitters such as glutamate to their receptors and facilitates the inhibitory effect of Ca on N-methyld-aspartate receptors (6). Mg is involved in neuronal functions and inhibits the facilitatory effects of Ca on synaptic transmission. It exerts a voltage dependent blockage of Nmethyl-Daspartate (NMDA) receptor channel (6). In this study, a significantly low serum Zn and Mg level was found in patients with febrile convulsion as compared with the controls. Similar findings have been reported earlier, which found that the mean serum concentration of Mg and Zn were significantly lower in the children with febrile convulsion (2, 3, 7, 8-10). In this line, the serum Zn level was found significantly lower in cases of simple febrile seizures than in controls (11, 12), while Sadeghzadeh et al. did not found any clear abnormalityin serum, Ca or Zn levels in children with FS although his study did not have a control group (13). In a casecontrol study, serum Zn level of cases was lower than that of controls; however, the reduction in its level was not statistically significant (14). Hypozincemia triggers the NMDA receptor which is one of the members of glutamate family receptors. It can stand to reason, therefore, hypozincemia may play an important role in initiation of epileptic discharge (14). In the current study, a significantly low Ca concentration was found in patients with febrile convulsion as compared with the controls and K concentrations were different in the two groups. Ca and K concentrations in the FS group were lower than in the control group (3). We found a significant difference between the mean serum sodium of children with FS and controls. This is contrary to Nadkarni et al. results (6) but in line with Heydarian et al.’s (15). While this was a case–control study with a sound design, it suffered from some shortcomings such as we did not perform the detection of CSF level of the trace elements.
In conclusion, serum Zn, Na, Ca, and Mg levels were significantly lower in children with simple febrileseizure in comparison with febrile children without seizure. It can emphasize the hypothesis that there is a relation between some serum elements’ levels and febrile seizure in children.
Acknowledgments
The authors want to thank the parents and the guardians of children who consented with the participation of their children in the study.
Author contribution
Mahmoud Zardast and KokabNamakin designed the research. All authors contributed in data gathering, data analysis, and preparing the manuscript. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of interest
None.
Funding Support
This research has been supported by Birjand University of Medical Sciences, Birjand, Iran.
References
- 1.Martindale JL, Goldstein JN, Pallin DJ. Emergency department seizureepidemiology. Emerg Med Clin North Am. 2011;29:15–27. doi: 10.1016/j.emc.2010.08.002. [DOI] [PubMed] [Google Scholar]
- 2.Lee J-H, Hyun Kim J. Comparison of Serum Zinc Levels Measured by Inductively Coupled Plasma Mass Spectrometry in Preschool Children with Febrile and Afebrile Seizures. Ann Lab Med. 2012;32:190–193. doi: 10.3343/alm.2012.32.3.190. http://dx.doi.org/10.3343/alm.2012.32.3.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Akbayram S, Cemek M, Büyükben A, Aymelek F, Karaman S, Yilmaz F, DoganM , Caksen H. Major and minor bio-element status in children with febrile seizure. BratislLekListy. 2012;113(7):421–423. doi: 10.4149/bll_2012_095. [DOI] [PubMed] [Google Scholar]
- 4.Johnston MV. Seizures in children. In: Behrman RE, JensonHB , Stanton BF, editors. Nelson Textbook of Pediatrics. 18thed. Philadelphia: Saunders; 2008. pp. 2457–73. [Google Scholar]
- 5.Salehiomran MR, Mahzari M. Zinc status in febrile seizure: a case-control study. Iran J Child Neurol. 2013;7(4):20–23. [PMC free article] [PubMed] [Google Scholar]
- 6.Nadkarni J, Binaykiya I, Sharma U, Dwivedi R. Role of serum sodium levels in prediction of seizure recurrence within the same febrile illness. Neurology Asia. 2011;16(3):195–197. [Google Scholar]
- 7.Ganesh R, Janakiraman L. Serum zinc levels in children with simple febrile seizure. ClinPediatr (Phila) 2008;47:164–166. doi: 10.1177/0009922807306165. [DOI] [PubMed] [Google Scholar]
- 8.WaqarRabbani M, Ali I, ZahidLatif H, Basit A, Rabbani MA. Serum zinc level in children presenting with febrile seizures. Pak J Med Sci. 2013;29(4):1008–11. [PMC free article] [PubMed] [Google Scholar]
- 9.Ehsanipour F, Talebi-Taher M, Harandi N, Kani K. Serumzinc level in children with febrile convulsion and itscomparison with that of control group. Iran J Pediatr. 2009:65–8. [Google Scholar]
- 10.Amiri M, Farzin L, Moassesi ME, Sajadi F. Serum trace element levels in febrile convulsion. Biol Trace Elem Res. 2010;135(1-3):38–44. doi: 10.1007/s12011-009-8487-6. [DOI] [PubMed] [Google Scholar]
- 11.Mohamed Aly IAR, Mohamed Kmal H, Soliman DR, Hassan Mohamed M. Iron profile parameters and serum zinc & copper levels in children with febrile convulsions in Banha. J Am Sci. 2014;10(7):1–4. [Google Scholar]
- 12.Gattoo I, Harish R, QuyoomHussain S. Correlation of serum zinc level with simple febrile seizures: a hospital based prospective case control study. Int J Pediatr. 2015;3(2):16. [Google Scholar]
- 13.Sadeghzadeh M, Nabi S, Khoshnevisasl P, Mousavinasab N. The correlation between cerebrospinal fluid and levels of serum zinc and Ca in children with febrile seizure. J ComprehensPediatr. 2013;3(5):179–83. [Google Scholar]
- 14.Osama N, Salah , Ehab R, Abdelraou , Marwa H, Abdelhameed Ahmed Dawood, Adel F, Kilany HA, Suzette I. Assessment of the Level of GABA and some trace elements in blood in children who suffer from familial febrile convulsions. Macedonian JMedSci. 2014;7(1):68–73. [Google Scholar]
- 15.Heydarian F, Ashrafzadeh F, Cam S. Simple febrile seizure: the role of serum sodium levels in prediction of seizure recurrence during thefirst 24 hours. Iran J Child Neurol. 2009;3(2):31–4. [Google Scholar]