Phenotypic spectrum and prognostic factors in epilepsy with eyelid myoclonia

Genetic generalized epilepsy (GGE) represents a common form of epilepsy both in adult and children’s cohorts. The International League Against Epilepsy recently provided a new classification framework distinguishing idiopathic generalized epilepsy (IGE) syndromes from other non-IGE syndromes within the context of GGE, in view of the strong overlap in terms of genetics, electroclinical features, and prognosis observed in the former group. If on the one hand previous studies thoroughly delineated the clinical characteristics of IGE, on the other still much work is needed to better define other non-IGE syndromes. Epilepsy with eyelid myoclonia (EEM) represents one of the most common non-IGE syndromes encountered in clinical practice and has been characterized by the classical triad of eyelid myoclonia with or without absences, photosensitivity, and eye closure sensitivity. Previous studies focusing on EEM have been conducted on small cohorts of patients revealing a marked clinical heterogeneity. In the present thesis, we will first provide an updated overview of the nosology and the electroclinical features of GGE syndromes, mainly focusing on EEM and discussing the major limitations of existing literature. Next, in the experimental part of the thesis, we will illustrate the results from three original studies conducted on the largest cohort of patients ever recruited so far. Indeed, during the past three years, we had the opportunity to coordinate an international study group including 20 epilepsy centers, which allowed us to enroll 267 EEM patients. We investigated the electroclinical features and the long-term seizure outcome of EEM, highlighting the existence of homogenous disease sub-phenotypes through the use of modern clustering techniques, and we underscored relevant clinical and prognostic differences based on sex. Finally, we will provide a unifying interpretation of our results, which support the hypothesis of EEM as a spectrum disorder, and we will discuss their implication in epilepsy care and research.