The effects of menarche on seizure burden in Lennox-Gastaut syndrome.

RATIONALE: Hormones such as estrogen and progesterone influence seizure thresholds resulting in catamenial epilepsy in a subset of women with epilepsy. While prior studies assessing the correlation between menarche and seizure onset have found mixed results, little is known about the effects of puberty on seizure burden in patients with developmental and epileptic encephalopathies, such as Lennox-Gastaut syndrome (LGS). Determining whether seizure burden in LGS is affected by pubertal changes such as menarche will inform prognosis and anticipatory guidance for caregivers of patients. METHODS: A single-center retrospective chart review of female patients with LGS who had a documented age of menarche and who had been evaluated at a single tertiary care children's hospital between 2013-2023 was performed. Menarche was used as a proxy for puberty. Seizure type, frequency, number of anti-seizure medications, and change in anti-seizure medications were recorded yearly between the ages of 5-21 years. Statistical analysis with cumulative logit mixed models was used to estimate the odds of a patient having higher seizure frequency by seizure type. A linear mixed model was used to assess change in antiseizure medications. RESULTS: A total of 22 patients met inclusion criteria. Menarche was not independently statistically significantly associated with increased overall seizure when controlling for age (OR 0.58, p = 0.195). However, age was independently positively associated with seizure frequency (OR 1.16 per year, p = 0.002). When controlling for age, most individual seizure types (non-motor, atonic, tonic, myoclonic, clonic, status epilepticus) did not significantly increase with menarche. Total number of antiseizure medications (ASMs) used significantly increased after menarche by an estimated 0.43 ASMs (p = 0.026), when controlling for age. CONCLUSIONS: After controlling for age, menarche in patients with LGS did not correlate with increased seizure frequency in total or if stratified by specific seizure types. However, overall seizure frequency and anti-seizure medication usage increased with age, suggesting a gradual worsening of epilepsy over adolescence. These data provide important information regarding the clinical course of LGS which may aid in both medical management and in anticipatory guidance for families as their children enter adolescence. Further study is needed for deeper understanding of long-term outcomes of LGS, and how age and puberty may affect seizures in males with LGS.