Spreading Depolarization and Seizures: End of the Beginning, or Beginning of the End?

Like Janus, the Roman god of beginnings, transitions, and endings, spreading depolarizations (SDs) can be depicted with two faces: one looking backward, waving a symbolic farewell to the end of a cortical seizure; the other forward looking, opening a darker door for a fatal wave in the brainstem that ends life. There is good agreement on the distinct electrical nature of both events, but neither role is yet proven in patients. SD is a slow-moving wave of cellular depolarization that steadily silences neuronal networks and depresses EEG amplitude, whereas seizures represent fast, intermittent synchronization of neural networks with highly variable EEG activation patterns. However, the thresholds triggering both events are neither fixed nor inseparable; indeed, their co-occurrence and interaction depend on dimly-lit intrinsic brain pathophysiology. New insights into single gene control of SD and seizure thresholds are beginning to illuminate the darkness. Here, we review recent data and consider the title's question at the end.