Neuroendocrine Response in Pediatric Febrile Seizures

Febrile seizures represent a common pediatric neurological emergency and are triggered by fever-related systemic stress rather than primary epileptic pathology. Acute febrile seizures are accompanied by activation of the hypothalamic-pituitary-thyroid axis and the sympathetic-adrenal system, resulting in measurable changes in circulating thyroid hormones and catecholamines. However, the magnitude and clinical relevance of this neuroendocrine response remain incompletely characterized.

This study is designed as a prospective, observational, case-control investigation conducted in a pediatric emergency department setting. Children aged 6 months to 5 years presenting with febrile seizures will be enrolled as the case group. An age-matched control group will consist of febrile children without seizures. Participants will not be assigned to any intervention, and all clinical management will follow standard care practices.

In the febrile seizure group, blood samples for measurement of serum thyroxine (T4), epinephrine, and norepinephrine will be obtained within 30 minutes after seizure cessation to capture the acute neuroendocrine stress response. Additional samples will be collected prior to hospital discharge to assess recovery-phase hormone levels. In the control group, blood samples will be collected during the febrile episode at the time of clinical evaluation. All laboratory analyses will be performed using validated methods under standardized conditions.

Clinical data collected will include demographic characteristics, fever features, seizure type and duration, recurrence during hospitalization, treatment administered, length of hospital stay, and requirement for pediatric intensive care unit admission. The primary objective is to evaluate associations between acute-phase neuroendocrine marker levels and seizure characteristics, particularly seizure duration and recurrence. Secondary objectives include comparisons between febrile seizure patients and febrile controls, as well as associations between hormone levels and clinical outcomes.

Statistical analyses will include descriptive methods, group comparisons using parametric or nonparametric tests as appropriate, correlation analyses, and multivariable regression models adjusting for relevant confounders such as age, sex, peak temperature, seizure type, and treatment exposure. The study aims to provide mechanistic insight into the neuroendocrine stress response associated with febrile seizures and to explore its potential relationship with disease severity and short-term outcomes.

Inclusion criteria

• Children aged 6 months to 5 years presenting to the pediatric emergency department with fever (documented at presentation or reported by caregiver within the preceding 24 hours).
• Case group: febrile seizure occurring in the context of a febrile illness.
• Control group: febrile illness without seizure, selected to be age-matched to cases (e.g., within ±6 months).
• Written informed consent obtained from a parent or legal guardian.

Exclusion criteria

• Suspected or confirmed central nervous system infection (e.g., meningitis, encephalitis).
• Prior diagnosis of epilepsy or history of afebrile seizures.
• Seizures attributable to acute metabolic derangements at presentation (e.g., significant hypoglycemia, clinically relevant electrolyte disturbances).
• Known thyroid disease or use of thyroid hormone/antithyroid medications.
• Known adrenal disorders or use of systemic catecholamine infusions at enrollment.
• Major chronic neurologic disorders or acute head trauma.
• Inability to obtain blood samples within protocol-defined time windows.