Cortical spreading depression (CSD) or spreading depolarization (SD) is a wave of electrophysiological hyperactivity followed by a wave of inhibition. Spreading depolarization describes a phenomenon characterized by the appearance of depolarization waves of the neurons and neuroglia that propagates across the cortex at a velocity of 1.5–9.5 mm/min. CSD can be induced by hypoxic conditions and facilitates neuronal death in energy-compromised tissue. CSD has also been implicated in migraine aura, where CSD is assumed to ascend in well-nourished tissue and is typically benign in most of the cases, although it may increase the probability in migraine patients to develop a stroke. Spreading depolarization within brainstem tissues regulating functions crucial for life has been implicated in sudden unexpected death in epilepsy, by way of ion channel mutations such as those seen in Dravet syndrome, a particularly severe form of childhood epilepsy that appears to carry an unusually high risk of SUDEP (sudden unexpected death in epilepsy).