ANALYSIS OF ORAL ASSOCIATION OF SERUM ZINC LEVEL WITH FEBRILE SEIZURES IN CHILDREN

: Introduction: Febrile seizures occur in young children at a time in their development when seizure threshold is low. They typically occur relatively early in an infectious illness usually during the rise of temperature curve. Aims and objectives: The basic aim of the study is to analyze the oral association of serum zinc level with febrile seizures in children of Pakistan. Material and methods: This study was conducted at Bahawal Victoria hospital, Bahawalpur during Jan 2018 to May 2018. The children of 1 year to 6 years were considered in this study. The patients who had any evidence of central nervous system infection, epilepsy, metabolic seizures or those who are already on zinc therapy for any other ailment like malnutrition, diarrhea, pneumonia or acrodermatitis enteropathica were excluded. Results: Frequency of low serum zinc level was 26% in children with febrile seizures. Sixty three (63%) children were between 6 months to 3 years of age while rest of the 37(37%) were between >3 years to 6 years of age. Upper respiratory tract infection was the most frequent cause of fever evident in 24 children (24%) followed by tonsillitis 17 (17%), pneumonia 16 (16%), urinary tract infection 16 (16%), otitis media 15 (15%), and bronchiolitis 12 (12%) in children having febrile seizures. Conclusion: It is concluded that low serum zinc levels are fairly sufficient to support the hypothesis that Zinc deficiency could be a potential risk factor for febrile seizure in children.


INTRODUCTION:
Febrile seizures occur in young children at a time in their development when seizure threshold is low. They typically occur relatively early in an infectious illness usually during the rise of temperature curve. Febrile seizures occur in common childhood infections such as infections of the respiratory system, otitis media, acute gastroenteritis, and children respond to these infections with comparably higher temperatures. The onset of febrile seizures generally follows a bell-shaped curve. 94% occur within the first three years of age and 6% after three years of age [1].
A seizure is a paroxysmal event caused by abnormal electrical discharge inside the brain. Febrile convulsion; twice as common in boys as in girls, is one of the most common type of seizure occurring in children between 5 months and 6 years of age, accounting for 30% of all seizures in children. This is an age dependent response of the immature brain to fever in children, who do not have an intracranial infection, metabolic disturbance, or history of afebrile seizures [2]. Eighty to eighty five percent febrile seizures occur between 6 months and 3 years of age, with peak incidence at 18 months. A child with a simple febrile seizure has potential for recurrence and 2-7% of children may develop epilepsy by adolescence. Contrary to simple febrile seizure, complex febrile seizures are prolonged (>15 minutes), focal and occur more than once in 24 hours [3].
Zn is as a co-factor of glutamate decarboxylase which is an enzyme needed for gamma-aminobutyric acid synthesis in the central nervous system and reduced CSF zinc levels have also been noted in febrile convulsions. Recent evidences indicate that zinc deficiency plays a significant role in febrile seizures. The following mechanisms can be postulated. Zinc increases storage capacity of glutamate or slows down the release rate of glutamate [4]. Zinc increases the activity of pyridoxine needed for pyridoxine formation reciprocally pyridoxine increases the activity of glutamate decarboxylase which results in gamma-aminobutyric acid syntheses. Thus, decreased zinc levels lowers GABA synthesis which would precipitate seizures. Persistent and prolonged seizure activity cause cerebral edema, hypoxia, hyperthermia, hypoglycemia and vasomotor instability [5]. Respiratory depression may ensue from involvement of respiratory centre or from drugs used for seizure control. Vomiting and aspiration of secretions also increase morbidity. Hence treatment should be taken precedence over investigation of the cause [6].

Aims and objectives
The basic aim of the study is to analyze the oral association of serum zinc level with febrile seizures in children of Pakistan.

MATERIAL AND METHODS:
This study was conducted at Bahawal Victoria hospital, Bahawalpur during Jan 2018 to May 2018. The children of 1 year to 6 years were considered in this study. The patients who had any evidence of central nervous system infection, epilepsy, metabolic seizures or those who are already on zinc therapy for any other ailment like malnutrition, diarrhea, pneumonia or acrodermatitis enteropathica were excluded.
Determination of Zinc levels 5cc blood was collected by venipuncture under strict aseptic precautions and sent to biochemistry laboratory for assessment of serum zinc levels. Determination of serum zinc levels was done by calorimetric method. The principle being zinc in alkaline medium reacts with nitro PAPS to give a purple color change. The intensity of the color formed depends in a direct relation to the levels of zinc found in the sample. Though earlier studies have established a linear relationship between serum zinc and CSF zinc in children with febrile seizures, CSF zinc analysis was not done in our study.

Statistical Analysis
The data was entered through a trained computer operator and imported into statistical package for social sciences (SPSS) version 17 for statistical analysis. Frequency distribution tables were produced with percentages.

RESULTS:
Frequency of low serum zinc level was 26% in children with febrile seizures. Sixty three (63%) children were between 6 months to 3 years of age while rest of the 37(37%) were between >3 years to 6 years of age. Low serum zinc level in different age groups is given in

DISCUSSION:
Febrile seizure is a common neurologic problem occurring in children aged between 6 months to 6 years. The etiology of febrile seizure is unknown but genetic factors or electrolyte disturbances may have a role in its occurrence or recurrence. To date, it is revealed that febrile seizures can be induced by several factors 7 . There is a hypothesis that febrile seizures arise due to excitation of the neurons during brain growth. This correlates with the most common age group in which this entity occurs. Gammaaminobutyric acid is an important inhibitory neurotransmitter [8].
Although its pathogenesis is debatable, studies have revealed that the genetic factors, family background, immunologic disorders, iron deficiency and zinc deficiency may play a role in febrile seizure. The infection state exhibits non-specific host responses, including immune responses such as changes in the concentrations of certain plasma proteins, cytokines (tumor necrosis factor, interleukin-1, interleukin-6) and interferon which may result in reduction of serum zinc level. Hypozincemia has been suggested as a possible change during the rising phase of body temperature in febrile patients [9]. Ganesh et al from Chennai, Lee et al, and Hitz et al also showed similar results. The serum zinc levels did not show any significant correlation with age of onset, gender, family history and nutritional status in this present study [10]. All previous studies have shown similar findings in this aspect. As serum zinc concentration in any population is influenced by factors such as dietary pattern, vitamin A, vitamin D deficiency, zinc levels in the soil and water, further studies are needed in this aspect to identify the probable cause for this finding [11].

CONCLUSION
It is concluded that low serum zinc levels are fairly sufficient to support the hypothesis that Zinc deficiency could be a potential risk factor for febrile seizure in children. Future research should be directed towards the therapeutic trial of zinc supplementation and formulate the zinc treatment regimen including its dose and duration.