An iEEG investigation on sex-specific differences in seizure duration

Male people with epilepsy (mPWE) are at higher risk for bilateral tonic-clonic seizures (BTCs) and sudden unexpected death in epilepsy (SUDEP) compared to female people with epilepsy (fPWE). Despite major clinical and personal implications, little is known about sex-specific differences in seizure propagation and termination. Characterization of seizure duration in men versus women with unifocal epilepsy.

Adults with unifocal epilepsy and available intracranial EEG (iEEG) recordings (September 2006 to March 2022) were identified retrospectively. Up to 20 clinical seizures were analyzed per person, excluding individuals with status epilepticus or lateralized periodic discharges. Seizure duration was determined based on iEEG recordings. In focal to bilateral tonic-clonic seizures (FBTCs), durations of the focal and BTC phases were assessed based on EEG and seizure semiology. Multiple linear regression was used to assess sex-specific differences in seizure duration, adjusting for age, epileptic hemisphere, frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), lateralizing signs, onset during sleep, and focal seizures with preserved consciousness and aura phenomena (FPC-a). A restricted-cohort sensitivity analysis was performed, excluding PWE in whom clinical seizure onset preceded iEEG onset.

A total of 100 PWE (m/f = 50/50; age: 33.6 ± 12.2 years) and 758 seizures (120 FBTCs) were analyzed. While fPWE had significantly longer focal seizures (FSs) (p = 0.015), mPWE revealed significantly longer FBTCs (p < 0.001), driven by a prolonged focal phase (p = 0.002). No significant difference was observed for the BTC phase. In the restricted cohort (n = 77 PWE), the prolongation of the focal phase during FBTCs in mPWE remained robust (p = 0.006).

Our findings demonstrate sex-specific differences in seizure duration, suggesting that seizure propagation may differ between men and women. This may contribute to a better pathophysiological understanding of the sex-specific differences in seizure manifestation and associated risks and underline the yet unmet need for a sex-specific approach in epilepsy research and patient management.

Sex-related differences in epilepsy are increasingly recognized but remain poorly understood. In this study, we compared seizure duration between women and men with unifocal epilepsy using intracranial brain recordings. We found that women had longer focal seizures, whereas men had longer focal phases in focal to bilateral tonic-clonic seizures. Further research is needed, as these differences may be relevant for clinical care and risk assessment in epilepsy.