Back to the Future: Endophenotypes of Idiopathic Generalized Epilepsy

Prodromal Phase of Idiopathic Generalized Epilepsy: A Register-Based Case Control Study. Gesche J, Rubboli G, Beier CP. Neurology 2024;103(8):e209921 Background and objectives: Idiopathic generalized epilepsy (IGE) is associated with distinct behavioral traits, symptoms of frontal lobe dysfunction, and psychiatric comorbidity. Whether psychiatric symptoms are part of the IGE endophenotype or secondary to the burden of chronic disease is unknown. In this study, we aimed at describing the sequence of appearance of psychiatric and epilepsy symptoms in patients with IGE. Methods: Inclusion criteria for this cohort study were diagnosis of IGE with age at diagnosis at 10–25 years. We created 2 mutually exclusive cohorts, 1 based on ICD-10 codes in Danish registers with a first IGE diagnosis from January 1, 2005, to December 31, 2018, and a second patient cohort treated at Odense University Hospital and the Danish Epilepsy Centre in the same period. Each case was matched with 10 age-matched, sex-matched, and geography-matched normal population controls from the Danish registers. We compared social status, health care utilization, and psychiatric diagnoses between the groups in the 5 years preceding epilepsy diagnosis, at diagnosis, and at the end of the study period using the Wilcoxon rank-sum test and confirmatory logistic regression models. Results: We identified 1009 patients for the register-based cohort (55.1% female; mean age at diagnosis [SD]: 15.9 [±3.8] years) and 402 patients for the hospital-based cohort (56.2% female; mean age at diagnosis [SD]: 18.3 [±7.4] years) and matched them to 10,090 and 4020 controls, respectively. IGE cohorts and controls did not differ at birth. In the 5 years before their IGE diagnosis, register patients had an increasing number of contacts with hospitals (mean visits [SD]: cases: 8.3 [±5.6], controls: 6.6 [±4.5]) and their general practitioners (mean visits [SD]: cases: 48.7 [±26.3], controls: 45.3 [±24.5]) and received more prescriptions for psychiatric medications (prescriptions: cases: 4.2%, controls: 2.5%, p = 0.003) compared with controls. Patients had a higher rate of psychiatric comorbidity (comorbidity: cases: 26.5%, controls: 17.8%, p < 0.0001) at the end of the study than controls. Data were similar in the hospital-based cohort. Discussion: Our data suggest a prodromal phase of IGE detectable approximately 5 years before the first seizure characterized by increased health care utilization and greater use of prescription medicine for psychiatric symptoms.