Developmental and epileptic encephalopathy in patients with epilepsy due to hypothalamic hamartomas.

Abstract

Objective: What factors influence cognition and behavior in patients with epilepsy caused by hypothalamic hamartoma (HH)?

Methods: We conducted a retrospective study of 103 patients referred to the Epilepsy Center in Freiburg, Germany, over the past 24 years. Analyzed parameters included development/intellectual functioning, behavior, seizure types and frequency, as well as electroencephalography (EEG) and magnetic resonance imaging (MRI) analyses.

Results: Half of the patients showed signs of global developmental delay (GDD) or intellectual disability (ID). Patients with GDD/ID were younger at epilepsy onset (p < .05) and at first referral (p < .001), had shorter disease durations (p < .01), experienced more frequent seizures (p < .001), and were prescribed more antiseizure medication (ASM; p < .01). They also had larger HH volumes (hamartoma types Delalande III and IV, both p < .001) and more frequent pathological EEG background activity (p < .001), as well as more extended interictal epileptiform discharges (IEDs; p < .05, the rate of IED and seizure types were comparable, p > .05). Of interest, pathological EEG background activity and HH type were the only predictors of GDD/ID resulting in a highly predictive model (R² = 0.75, p < .001). Patients with GDD/ID also experienced more externalized behavioral problems, particularly aggression, which was predicted only by EEG background activity (R² = 0.36, p < .001). None of the epilepsy-specific parameters, such as duration and seizure type or frequency, were significant predictors.

Significance: Our findings support the idea that patients with epilepsy due to HH and GDD/ID may have a more severe underlying condition with a likely genetic etiology, characterized by developmental and epileptic encephalopathy.