# Rethinking the classification of acute status epilepticus: structural brain vs. systemic etiologies

## TL;DR

This paper proposes a new classification for acute status epilepticus based on whether it arises from brain injury or systemic causes, which could improve treatment and outcomes.

## Contribution

The paper introduces a refined etiological classification of acute SE that distinguishes structural from systemic causes.

## Key findings

- Structural causes of SE are linked to higher mortality and greater seizure recurrence.
- Systemic causes primarily involve transient disruptions in brain function.
- Differentiating these etiologies may guide ASM therapy and prevent chronic epilepsy.

## Abstract

Status epilepticus (SE) is a life-threatening neurological emergency whose modern conceptualization employs a multidimensional framework encompassing semiology, etiology, electroencephalographic features, and age. Among these, the etiological dimension is central, as it captures the underlying pathophysiology and critically informs both acute management and long-term prognosis. Current classifications define acute SE by its temporal proximity to a central nervous system insult, yet this approach groups heterogeneous mechanisms under a single category. Acute SE arising from structural brain injury involves downstream receptor and ionic dysfunction driven by inflammation, neuronal loss, glial activation, and network remodeling. In contrast, systemic etiologies, such as electrolyte disturbances, toxic exposures, or withdrawal states, primarily reflect transient disruptions in excitatoryinhibitory balance or ionic homeostasis. These mechanistic distinctions translate into meaningful clinical differences: structural causes are associated with higher mortality, greater seizure recurrence, and an increased risk of subsequent epilepsy. A more refined etiological classification distinguishing structural from systemic causes could better capture variations in pathophysiology, treatment response, and long-term outcomes. Such a framework may also guide decisions regarding the duration and intensity of antiseizure medication (ASM) therapy, a domain in which evidence remains limited. Whether early and sustained ASM treatment after SE due to structural brain injury can modify epileptogenesis is unknown, as no randomized controlled trials have directly addressed this question. Clarifying etiological subgroups may therefore facilitate targeted clinical and translational studies, improve prognostication, and ultimately support the development of interventions to prevent the transition from acute SE to chronic epilepsy.