Refractory focal epilepsy evolving into a Lennox-Gastaut syndrome-like

Patients with focal epilepsy may over time experience a significantly unfavorable progression, developing an electroclinical profile that meets some or all criteria for Lennox-Gastaut syndrome (LGS). This study aimed to describe the electroclinical characteristics of these patients, whom we referred to as patients with LGS-like, and to determine their common and distinguishing features compared to classical LGS.

We retrospectively examined 2,130 adult-patients who underwent video-EEG monitoring from 2002 to 2024. LGS-like was defined as focal epilepsy with over the disease's course: (1) a clinically unfavorable progression, (2) the development of generalized paroxysmal fast activity (GPFA) on EEG, and (3) another LGS criteria: tonic/atonic seizures, and/or cognitive and/or behavioral regression, and/or diffuse slow spike-and-wave (SSW) activity. Patients with LGS-like were classified into full or partial spectrum based on whether or not they met all the criteria for LGS.

Thirty-four patients (1.6%) met the criteria for LGS-like syndrome (median age at seizure onset: 10.5 ± 6.9 years [range 1-33]; median epilepsy duration: 15.5 ± 11 years [range 1-45]). Among them, 21 patients had tonic seizures, three had atonic seizures, and one exhibited both. Eight patients showed cognitive and/or behavioral regression, while 29 patients displayed diffuse SSW patterns. Seven patients (20.5%) fulfilled the criteria for full-spectrum LGS. Compared with classical LGS, patients with LGS-like showed distinct features: (1) later seizure onset, (2) lower rate of cognitive regression (23.5%), (3) predominantly asymmetric tonic seizures and focal seizures during GPFA (62%), (4) frequent asymmetric GPFA (50%) and GPFA during wakefulness (53%), (5) high rate of SSW at adulthood (85%), though mostly asymptomatic, (6) normal EEG background activity (91%), and (7) favorable outcomes in 69% of cases. The only distinguishing factor between full-spectrum and partial-spectrum LGS was disease severity at the time of video-EEG: all full-spectrum LGS patients (100%) experienced daily seizures, compared with 55.6% of partial-spectrum patients (p = 0.0036). The similar favorable outcome in both groups (71% vs. 68%, p = 0.7) highlight the potential reversibility of the processes underlying LGS-like, regardless of the number of LGS diagnostic criteria met.

The evolution from focal epilepsy to a syndrome that met some or all criteria for LGS supports the existence of a pathological continuum between the underlying epileptic networks. Early identification of such patients may enable timely therapeutic adaptation and help prevent unfavorable outcomes.