Abstracts

Rationale: Between-sex differences have been identified in drug pharmacokinetics and drug-induced adverse effects. Yet, anti-seizure medication (ASM) efficacy differences among women versus men have not been described. Herein, we tested for sex differences in valproate’s (VPA) suppression of the photoparoxysmal response in naïve females versus males.

Methods: We analyzed prospectively-acquired EEG data from sequential photosensitive ASM-naïve patients before and after VPA treatment. Patients were tested according to European guidelines (see ILAE website). The test-retest IPS procedure period was limited to 1.5 years, most however between 6-12 wks. Only generalized PPRs were considered positive. Hz ranges were transformed into standardized photosensitivity range (SPR). An SPR value >3 was defined as VPA clinical response, a criteria used in Proof-of-Principle trials. Blood samples were collected to measure total plasma [VPA] concentration, shortly after several patient’s EEG, when dictated by clinical need.

Results: Forty-eight patients (27F, 21M; age range 8-50 yr) met our criteria. Plasma [VPA] concentrations were known in 13 patients (average 67 mg/L, range=37-124). Males showed in all cases (21/21) a SPR decrement of at least 3, whereas females in 14/27 (51.85%) (p=0.0001) with PPR elimination in respectively 10/21(47.6%) versus 4/27 (14.8%). The median plasma total [VPA] concentrations was 51 mg/L in 5 male responders, 98 mg/L in 4 female responders and 99 mg/L in 4 female non-responders.
Thirty percent of young girls and 41 percent of older females were VPA non responders.

Conclusions: In 48 ASM-naïve patients with epilepsy plus photosensitivity, we found that all IPS-tested males suppressed PPR with VPA treatment compared to only half of the females.  VPA doses nor [VPA] concentrations could explain this between-sex difference.

Funding: No funding.