references) using comprehensive electronic search strategies combining terms "epilepsy", "seizures", "prediction", "forecasting", "cycles", "patterns", "circadian", and "multidien", with no language restrictions. Identified studies used different outcome measures, but most involved analyses of electroencephalography (EEG) to predict seizures minutes in advance, with variable success. A single prospective trial of an implanted device for chronic EEG demonstrated abovechance accuracy of warnings for imminent seizures in 9 out of 15 enrolled subjects. Two studies in independent cohorts of subjects chronically implanted with intracranial electrodes showed that rates of interictal epileptiform activity oscillate in circadian and multiday (multidien) cycles that help determine seizure likelihood. Circadian cycles and seizure diaries were used in three studies to forecast seizures over short horizons, but we found no results on forecasting seizures several days in advance. Added value of this study:In a large cohort of people with drug-resistant focal epilepsy who had chronic EEG recorded by an approved clinical device, we demonstrate that circadian and multidien cycles can be leveraged to forecast seizures up to three days in advance in some subjects and 24 hours in advance in the majority of subjects. These results highlight the feasibility of seizure forecasting over horizons longer than previously possible. Implications of all the available evidence: Seizures are not entirely random events. Using cyclical patterns of brain activity to forecast seizures hours to days in advance may enable novel seizure warning systems and prevention strategies. Convergence of findings from multiple independent datasets suggests the generalizability of this approach in people with epilepsy, though this will require direct testing in prospective clinical trials.

IMPORTANCEFocal epilepsy is characterized by the cyclical recurrence of seizures, but, to our knowledge, the prevalence and patterns of seizure cycles are unknown.OBJECTIVE To establish the prevalence, strength, and temporal patterns of seizure cycles over timescales of hours to years.

The cyclical organization of seizures in epilepsy has been described since antiquity. However, historical explanations for seizure cycles—based on celestial, hormonal, and environmental factors—have only recently become testable with the advent of chronic electroencephalography (cEEG) and modern statistical techniques. Here, factors purported over millennia to influence seizure timing are viewed through a contemporary lens. We discuss the emerging concept that seizures are organized over multiple timescales, each involving differential influences of external and endogenous rhythm generators. Leveraging large cEEG datasets and circular statistics appropriate for cyclical phenomena, we present new evidence for circadian (day‐night), multidien (multi‐day), and circannual (about‐yearly) variation in seizure activity. Modulation of seizure timing by multiscale temporal variables has implications for diagnosis and therapy in clinical epilepsy. Uncovering the mechanistic basis for seizure cycles, particularly the factors that govern multidien periodicity, will be a major focus of future work.