Post-Stroke Epileptogenesis as a Dynamic Network Process: State-Dependent Biomarkers, Longitudinal Monitoring, and...

Post-stroke epilepsy (PSE) is one of the most common long-term neurological complications of stroke and represents a major contributor to disability, reduced quality of life, and increased healthcare burden. Although numerous risk factors and biomarkers have been proposed, many current risk models still emphasize lesion-related predictors and do not fully account for the temporal evolution of post-stroke network excitability. This narrative review aims to examine post-stroke epileptogenesis as a dynamic process of network reconfiguration and to summarize current evidence on biological, neurophysiological, imaging, and clinical biomarkers across different stages following stroke. A structured narrative review of the literature was performed using major biomedical databases. Studies addressing mechanisms of post-stroke epileptogenesis, biomarkers, network dysfunction, neuroinflammation, EEG findings, neuroimaging correlates, and longitudinal monitoring strategies were evaluated and synthesized qualitatively. Evidence suggests that post-stroke epileptogenesis is driven by complex interactions among structural injury, neuroinflammation, blood-brain barrier dysfunction, neurotransmitter imbalance, maladaptive plasticity, and large-scale network reorganization. Importantly, many biomarkers demonstrate substantial temporal variability, and their clinical significance depends on the stage of recovery and the evolving state of brain networks. Emerging data indicate that sleep disturbances, stress, mood disorders, metabolic factors, and other state-dependent influences may further modulate seizure susceptibility after stroke. Post-stroke epileptogenesis may be better conceptualized as a dynamic process of network instability rather than a fixed consequence of focal brain damage. It is proposed that the post-stroke brain can transiently or persistently enter an "irritable brain state", characterized by increased vulnerability to pathological synchronization under the influence of biological and behavioral modulators. This framework may facilitate the development of longitudinal biomarker strategies and personalized monitoring approaches in future research. However, it should be emphasized that the "irritable brain state" remains a conceptual and hypothesis-generating construct; no validated diagnostic criteria exist, and prospective evidence demonstrating that interventions targeting this state reduce the incidence of post-stroke epilepsy is currently lacking.