Epileptogenesis

Definition

Epileptogenesis is defined as a gradual process by which changes occur in the brain after a precipitating injury or insult which lead to development of epilepsy.

Etiology of Epileptogenesis

-Anything that causes epilepsy causes epileptogenesis, because it is the process of developing epilepsy

-The causes of epilepsy are: genetic, structural/metabolic, or unknown

-Structural/ Metabolic causes of epilepsy include

• neurodegenerative diseases
• traumatic brain injury
• stroke
• brain tumor
• infections of the central nervous system

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
• neurogenesis.

-These changes cause neurons to become hyperexcitable and can lead to spontaneous seizures.

-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 {*}

Neural reorganization

• pyramidal neurons are lost, and new synapses are formed
• loss of inhibitory neurons, such as GABAergic interneuron causing hyperexcitability {*}

Glutamate receptor activation

• activation of Glutamate receptors on the surfaces of neurons is involved in epileptogenesis {*}

Blood brain barrier disruption

• Blood brain barrier (BBB) disruption may cause post injury epilepsy
• albumin leaks from the blood into the brain parenchyma and induces epileptogenesis by activation of the transforming growth factor beta receptor on astrocytes {*}
• Iron from extravasated hemoglobin can lead to the formation of free radicals that damage cell membranes and has been linked to epileptogenesis {*}

Stages

The initial insult is typically followed by an acute seizure and then a latent or silent period without any overt seizures. In the next stage, a definitive stage is reached. It is marked by the emergence of seizures that are spontaneous or with an increase in the frequency of seizures.

References:

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588129
• https://en.wikipedia.org/wiki/Epileptogenesis#Pathophysiology
• Youman and Winn Neurological Surgery
• Rakhade, S. N., & Jensen, F. E. (2009). Epileptogenesis in the immature brain: emerging mechanisms. Nature reviews. Neurology, 5(7), 380–391. https://doi.org/10.1038/nrneurol.2009.80

{*} – important points