Causes[edit]
The causes of epilepsy are broadly classified as genetic, structural/metabolic, or unknown.[4] Anything that causes epilepsy causes epileptogenesis, because epileptogenesis is the process of developing epilepsy. Structural causes of epilepsy include neurodegenerative diseases, traumatic brain injury, stroke, brain tumor, infections of the central nervous system, and status epilepticus (a prolonged seizure or a series of seizures occurring in quick succession).[5]
Latent period[edit]
After a brain injury occurs, there is frequently a "silent" or "latent period" lasting months or years in which seizures do not occur;[6] Canadian neurosurgeon Wilder Penfield called this time between injury and seizure "a silent period of strange ripening".[7] During this latent period, changes in the physiology of the brain result in the development of epilepsy.[6] This process, during which hyperexcitable neural networks form, is referred to as epileptogenesis.[6] If researchers come to better understand epileptogenesis, the latent period may allow healthcare providers to interfere with the development of epilepsy or to reduce its severity.[6]
Treatment[edit]
A major goal of epilepsy research is the identification of therapies to interrupt or reverse epileptogenesis. Studies largely in animal models have suggested a wide variety of possible antiepileptogenic strategies although, to date, no such therapy has been demonstrated to be antiepileptogenic in clinical trials.[18] Some anticonvulsant drugs, including levetiracetam and ethosuximide have shown promising activity in animal models. Other promising strategies are inhibition of interleukin 1β signaling by drugs such as VX-765; modulation of sphingosine 1-phosphate signaling by drugs such as fingolimod; activation of the mammalian target of rapamycin (mTOR) by drugs such as rapamycin; the hormone erythropoietin; and, paradoxically, drugs such as the α2 adrenergic receptor antagonist atipamezole and the CB1 cannabinoid antagonist SR141716A (rimonabant) with proexcitatory activity. The discovery of the role played by TGF-beta activation in epileptogenesis raised the hypothesis that blocking this signaling may prevent epileptogenesis. Losartan, a commonly used drug for the treatment of hypertension was shown to prevent epilepsy and facilitate BBB healing in animal models. Testing the potential of antiepileptogenic agents (e.g. losartan) or BBB healing drugs necessitates biomarkers for patients selection and treatment-followup.[19] BBB disruption imaging was shown capacity in animal model to serve as a biomarker of epileptogenesis [20] and specific EEG patterns were also shown to predict epilepsy in several models.[21]
History[edit]
Throughout most of history for which written records exist on the subject, it was probably generally believed that epilepsy came about through a supernatural process.[22] Even within the medical profession, it was not until the 18th century that ideas of epileptogenesis as a supernatural phenomenon were abandoned.[22] However, biological explanations have also long existed, and sometimes explanations contained both biological and supernatural elements.[22]
Research[edit]
Epileptogenesis that occurs in human brains has been modeled in a variety of animal models and cell culture models.[2] Epileptogenesis is poorly understood,[6] and increasing understanding of the process may aid researchers in preventing seizures, diagnosing epilepsy,[23] and developing treatments to prevent it.[2]