Abstract
Hypersynchronous and exaggerated neuronal firing, exemplified by epileptiform activity and seizures, are disruptors of brain function across acute and chronic neuropathological conditions. Here, we focus on how seizure activity, whether as a primary symptom or a secondary comorbid event within a complex pathological setting, adversely impacts neurological trajectories. We discuss experimental and clinical evidence illustrating the participation of neurodegenerative and senescence-like adaptations. Paroxysmal neuronal events, through bidirectional causality, are linked with immune and microvascular changes, disrupting cellular homeostasis and creating a feed-forward loop that intertwines with age-related frailty to deteriorate mental health. We emphasize the clinical significance of early detection of these brain vulnerabilities through biomarkers, monitoring neurodevelopmental risks in children, and tracking neurodegenerative disease progression in aging populations.