Do Seizures Damage the Brain ?—Cumulative Effects of Seizures and Epilepsy: A 2025 Perspective

In 1885, William Gowers proposed that epilepsy is a progressive disease, based on clinical evidence before any effective treatments were available. His long-standing hypothesis has been summarized with the statement "seizures beget seizures." Whether this is the case and related questions about seizure-induced modification and damage of brain circuits are of fundamental importance for neurobiological understanding of epilepsy, development of effective treatment strategies, clinical management, and prognostication. Consensus about progression and seizure-induced damage has remained controversial. Here, we critically review these long-standing questions, incorporating perspectives about perceived inconsistencies in past studies, potential implications of recent longitudinal imaging and cognitive studies, and emphasize experimental and clinical gaps that have proved challenging. Answers to these questions are important for development of management strategies to achieve prompt effective acute control of seizures and prevention of their potential recurrence and long-term comorbidities.