Epileptogenesis

Source: Wikipedia, the free encyclopedia.

Epileptogenesis is the gradual process by which a typical

neurons to fire in an abnormal, hypersynchronous manner, known as a seizure.[3]

Causes

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

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]

Pathophysiology

Changes that occur during epileptogenesis are poorly understood but are thought to include cell death, axonal sprouting, reorganization of neural networks, alterations in the release of neurotransmitters, and neurogenesis.[5] These changes cause neurons to become hyperexcitable and can lead to spontaneous seizures.[5]

Brain regions that are highly sensitive to insults and can cause epileptogenesis include temporal lobe structures such as the hippocampus, the amygdala, and the piriform cortex.[6]

Neural reorganization

In addition to chemical processes, the physical structure of neurons in the brain may be altered. In

pyramidal neurons are lost, and new synapses are formed.[3]

Hyperexcitability, a characteristic feature of epileptogenesis in which the likelihood that

GABAergic interneurons, that would normally balance out the excitability of other neurons.[3] Neuronal circuits that are epileptic are known for being hyperexcitable and for lacking the normal balance of glutamatergic neurons (those that usually increase excitation) and GABAergic ones (those that decrease it).[6] In addition, the levels of GABA and the sensitivity of GABAA receptors to the neurotransmitter may decrease, resulting in less inhibition.[3]

Another proposed mechanism for epileptogenesis in TBI is that damage to white matter causes hyperexcitability by effectively undercutting the cerebral cortex.[8]

Glutamate receptor activation

It is believed that activation of

Src and Fyn that may lead to epileptogenesis.[2]

Excessive release of the neurotransmitter

Blood brain barrier disruption

Pathogenic influence was attributed also to the extravasation of other blood born substances such as
free radicals that damage cell membranes; this process has been linked to epileptogenesis.[17]

Treatment

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.

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.
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

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

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]

See also

References

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  3. ^ a b c d e Armijo JA, Valdizán EM, De Las Cuevas I, Cuadrado A (2002). "Advances in the physiopathology of epileptogenesis: Molecular aspects". Rev Neurol (in Spanish). 34 (5): 409–29.
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