Valproate impact and sex-dependent seizure remission in patients with idiopathic generalized epilepsy

• Published in: Journal of the neurological sciences Vol. 415; p. 116940
• Main Authors: Cerulli Irelli, Emanuele, Cocchi, Enrico, Morano, Alessandra, Casciato, Sara, Fanella, Martina, Albini, Mariarita, Fisco, Giacomo, Barone, Francesca A., Orlando, Biagio, Mascia, Addolorata, Manfredi, Mario, Fattouch, Jinane, Giallonardo, Anna T., Di Gennaro, Giancarlo, Di Bonaventura, Carlo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-08-2020
• Subjects: Adolescent; Adult; Anticonvulsants - therapeutic use; Childbearing age; Epilepsy, Generalized - drug therapy; Female; Gender medicine; Genetic generalized epilepsy (GGE); Humans; IGE prognosis; Male; Middle Aged; Retrospective Studies; Seizures - drug therapy; Treatment Outcome; Valproate restriction; Valproic Acid - therapeutic use; Young Adult; Gender medicine; IGE prognosis; Genetic generalized epilepsy (GGE); Valproate restriction; Childbearing age
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2020.116940

Idiopathic Generalized Epilepsy (IGE) management has become increasingly challenging due to the restricted use of Valproate (VPA) in females. The aim of the study was to assess possible differences in terms of seizure outcome between men and women suffering from IGE.
A cohort of IGE patients (age range: 13–50 years) followed from 1980 to 2018 were included. Their medical history was retrospectively reviewed to investigate possible factors influencing seizure outcome. Seizure Remission (SR) was defined as the absence of any seizure type over 18 months prior to the last medical observation. The primary outcome was to evaluate sex differences in terms of SR at last observation. A multivariable logistic regression model was elaborated using SR as dependent variable.
Three-hundred and sixty patients were included, 204 (56.7%) of whom were women. The median age at the end of follow-up was 30. At last medical observation, fewer women were receiving VPA compared with men (females 39.7% vs males 79.5%, p < .001). Overall SR was 70.6%. SR was significantly different according to sex (females 62.3% vs males 81.4%, p < .001). Multivariable logistic regression model showed that female sex (Odds Ratios [OR] = 0.52, 95% Confidence Interval [CI] = 0.29–0.94; p = .03), VPA treatment at last observation (OR = 0.44, 95% CI = 0.25–0.76; p = .003) and epilepsy syndrome (p < .001) were the factors independently associated with SR.
Recent modifications in VPA prescribing patterns may have determined a worse seizure control among IGE female patients. Comparative clinical trials assessing the best therapeutic options for women with childbearing potential are urgently needed.
•Therapeutic management is challenging in IGE female patients of childbearing age.•Given the limitations in VPA use, we investigated sex differences in seizure outcome.•We found a significant difference in VPA use between females and males.•VPA dosage and blood level were also found to differ according to gender.•Male sex and VPA use were independently associated with a better seizure outcome.