Generalized absence seizures: Where do we stand today?

Abstract

Generalized absence seizures are discussed here with respect to changing scientific concepts and newer findings, challenging the strict dichotomy of “generalized” vs. “focal” which may be counterproductive to the development of new ideas and treatments. Data from semiology, structural, and functional studies using quantitative electroencephalography (EEG), video-EEG monitoring, magnetoencephalography, magnetic resonance imaging, and positron emission tomography as well as neuropathology suggest a nosological spectrum from focal to generalized seizure-generating mechanisms. The terms “focal” and “generalized” as used to describe seizures represent abstractions and idealizations rather than ontological entities. The new terminology and classification of the ILAE (2017), despite its enormous merits, unfortunately also facilitates and fosters reductionist thinking, which may be pragmatic from a utilitarian perspective, but risks hindering scientific developments for the future. For instance, the seizure semiology of absences as a paradigmatic generalized seizure type is now classified as “non-motor seizure.” A detailed phenomenological analysis reveals that motor activity is an integral part of this seizure type. Many motor and so-called automatic absence symptoms can be understood as correlated elements of a general organization plan of the cortex. Corresponding functional and structural changes seen in imaging and high-resolution electrophysiology studies indicate focal contributions to seizure generation and a combination of focal and generalized features. Functional findings indicate that the frontal lobe with its projections to other brain areas may play an important role in generalized absence seizures. In this critical review we assess the evolution of pathophysiological concepts through the ages and present new research approaches for diagnosis and treatment.

Ictal hand signs: Minimal previous attention to these diagnostic indicators

“…The ILAE-classified generalized seizures, such as in absence seizures, show a temporal evolution of discrete signs, whereby they exhibit a "cranio-caudal march" [27]. This phenomenon has been discussed in the context of the current comprehension of network involvement in "generalized" seizures [28]. The limitations of using ictal semiology for localization are the absence of initial ictal signs (such as hand postures) and the onset of epileptic discharges in the "silent brain regions."…”

Neurophysiological signatures of visual attention in absence epilepsy and mild traumatic brain injury

“…Eye movements are a fundamental component of visual attention and they share multiple neural networks [14,15,16]. Notably, the frontal eye fields (FEFs) play a primary role in various aspects of eye movement, including preparation, initiation, visual orientation, awareness, perceptual performance, and conscious access [15,17]. Eye movements are not solely triggered by sensory error signals, such as retinal motion or displacement of peripheral details, but rather constitute a response to a multifaceted representation of the visual world encompassing objects, the visual scene, plans, goals, interests, and expectations about future events [18].…”

“…Absence seizures affect 10% to 17% of all cases of pediatric epilepsy [159]. Absences usually manifest behaviorally through staring and poor responsiveness, which are the most prominent symptoms of absence epilepsy [98,17,100]. Characteristically, absences impact eye movements and visual attention [160,35,28,161], i.e., the selection of visual stimuli based on spatial location and visual characteristics [4].…”

“…Several neural networks are involved in attention and eye movements [14,15]. In particular, the frontal eye field (FEF) has a leading function in eye movement preparation and triggering, but also in visual orientation, awareness, perceptual performance, and conscious access [15,17]. Given its functional characteristics and the predominance of ocular symptoms in absence seizures, the FEF may play a role in the symptomatology of absences [17].…”

“…In particular, the frontal eye field (FEF) has a leading function in eye movement preparation and triggering, but also in visual orientation, awareness, perceptual performance, and conscious access [15,17]. Given its functional characteristics and the predominance of ocular symptoms in absence seizures, the FEF may play a role in the symptomatology of absences [17]. Among the key regions of visual attention, frontal areas and thalamic nuclei (e.g., reticular nuclei and relay nuclei) are involved in the generation of absence seizures, too [170,171].…”