True seizures are a result of abnormal electrical activity in the brain, and are rare in horses. Brain trauma or any disease process that affects the brain can result in seizures. Epilepsy is abnormal brain electrical activity without any underlying cause known. Seizure-like activity can also occur at the end stage of any severe acute disease, i.e. when a horse is dying. The distressed activity of a horse in abdominal pain (colic) is sometimes confused with seizure.

Probably the most common occurrence of seizure follows an attempt at intravenous (IV) injection of a medication. Seizure results from accidental injection of a medication into the carotid artery, which lies immediately deep to the jugular vein and carries blood directly to the brain.

Horses that experience generalized seizures usually fall down on their sides and paddle with their limbs. Their neck is extended rigidly, and their third eyelids cover their eyes. Typically a horse seems unaware of its surroundings, their breathing is labored or shallow, and they may urinate or defecate uncontrollably. In a localized seizure, a particular body part violently or uncontrollably shakes or twitches. Many seizures are short-lived and the horse may get back to its feet. Often, horses are wobbly and weak in the minutes following an episode.