Rationale: Endogenous factors may trigger hormonal and neurotransmitter changes that lead to seizures. We hypothesized that preictal changes in stress hormone levels are biomarkers of impending seizures.
Methods:
Eighteen children with drug-resistant epilepsy (DRE) provided salivary samples during their phase I presurgical evaluation. Daily samples were collected every 2-3 hours, immediately placed in a -80C freezer and assayed for cortisol and alpha-amylase (a stable salivary proxy for catecholamines). Demographic information, epilepsy etiology and number (and times) of seizures were also collected. Time between each seizure (the event) and the closest sample was estimated. A time-to-event analysis was conducted using a mixed-effects Cox proportional hazards model, to account for multiple seizures and repeated measures per patient, and include adjustments for age and sex.
Results:
Six females and 12 males were analyzed (median (IQR) age 15.7 (3.0) years). Five (28%) had unknown epilepsy etiology, 5 (28%) had malformations of cortical development and eight (44%) had acquired lesions. Across patients, median (IQR) number of samples was 23 (7), and median (IQR) number of seizures was 4 (4). A total of 147 seizures were analyzed. Median (IQR) time from sample to seizure was 4.1 (1.1) hours. Higher preictal cortisol but not alpha amylase levels were associated with a higher risk of seizures (log-hazard rate = 1.27, 95% confidence interval (CI) = [1.15, 1.40], p< 0.001). There were no sex or age related differences (p >0.70).
Conclusions:
In children with DRE, seizures may be preceded by significant changes in cortisol hours prior to ictal events, reflecting a potential physiological relationship between stress and seizures. This finding has important clinical implications, as stress is a modifiable factor. Furthermore, preictal cortisol should be further evaluated as a reliable predictor of impending seizures.
Funding: This study was funded by the National Institute of Neurological Disorders and Stroke, award R03NS119799.