Abstracts

Rationale: Lennox Gastaut Syndrome (LGS) is a developmental epileptic encephalopathy with onset in childhood, typically before the age of 8 years. Electro-clinical features include multiple refractory seizure types (tonic, atypical absence, atonic, and myoclonic), intellectual disability, and scalp EEG findings of generalized paroxysmal fast activity (GPFA) and slow spike-wave complexes (SSW). These electro-clinical findings in LGS suggest a bilateral diffuse brain network activation, especially attention and default mode, but localized cortical lesions can also present with similar electrographic findings. Hence, the term Lennox-Gastaut Phenotype (LGP) was coined to encompass patients with most of the electrographic features of LGS, but with an older age of onset / minimal background slowing / mild intellectual disability / mildly asymmetrical electrographic findings with or without an underlying focal lesion. In such cases, resection of the focal lesion can aid in seizure cessation and normal development. Our study aims to differentiate the electro-clinical profile of focal epilepsy with LGP from LGS, as epilepsy surgery in the former may result in seizure freedom.

Methods: A retrospective pilot study of five patients referred to a single provider clinic for “refractory epilepsy secondary to LGS” from 2014 to 2021. Data on the age of seizure onset, cognitive profile, seizure semiology, electrographic findings, anti-seizure medication (ASM) at the time of referral, multimodal neuroimaging (MRI, FDG-PET, ictal SPECT, Volume-based morphometry), and outcomes were extracted from chart review and compared with the LGS electro-clinical profile.

Results: All patients fit the clinical profile of LGS based on the age of onset, cognitive status, and multiple seizures. Seizure semiology, multimodal imaging, and surgical outcome are shown in Table 1. Regarding the EEG, all patients had SSW and GPFA. Three patients had focal findings on the EEG and had similar semiology during their lifespan which indicated activation of a focalized network. Semiology was consistent with asymmetric bilateral features and focal motor symptoms. Multimodal imaging was concordant with focal epilepsy. Two out of 3 patients with focal semiology underwent surgical resection {one of them after SEEG} leading to seizure freedom and neurocognitive recovery, while one is awaiting an invasive evaluation.

Conclusions: Patients with LGP can be differentiated from LGS by the presence of a seizure semiology that activates the same focal neural network, even with minor variations in the semiology. LGP patients also lack other seizure types (atypical absence, myoclonic, and atonic seizures). Multimodal imaging is supportive of focal epilepsy even in the absence of a clear lesion in LGP. These patients should undergo epilepsy surgical evaluation, as early surgical intervention can lead to better clinical outcomes (seizure freedom, improved cognition, and limited ASM administration). Future directions: These findings will be applied to a larger sample of patients who are LGS and LGP to determine what electro-clinical features would aid in differentiating surgical versus non-surgical candidates. 

Funding: None