Epilepsy pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Overview[edit | edit source]

It is understood that epileptic seizure is the result of uncontrolled unusual synchronized, localized or widely distributed neuronal electrical discharges. The underlying event in all types of seizures is the paroxysmal depolarization shift (PDS) which also causes the EEG changes. In a normal circumstance we have a refractory period after every action potential, but in PDS, the absence of refractory period causes a prolonged membrane depolarization. In order to cause a seizure, so many PDSs most happen in the same time. Any alternation in a synaptic characteristics such as amount of neurotransmitters, function of inhibitory neurons, function of excitatory neurons, synaptic structure and ion channels involved in neurotransmitter release and conduction of action potential can prone a person to epilepsy. In focal epilepsy, epileptiform activity starts in a specific area of brain. It can further spread and cause secondary generalized seizure. In generalized epilepsy seizures occur in both cerebral hemispheres simultaneously or spread so fast from one to another that in EEG, we can see bilateral epileptiform activity from the start.

Pathophysiology[edit | edit source]

Physiology[edit | edit source]

• The normal physiology of neuronal action potential can be understood as follows:

• When an action potential reaches the plasma membrane of a neuron cell, voltage gated Na+ channels will open and Na+ flows into the cell and makes it depolarized.
• When plasma membrane potential reaches a specific level, K+ channel opening will hyperpolarize the neuronal membrane.^[1]

Pathogenesis[edit | edit source]

• It is understood that epileptic seizure is the result of uncontrolled unusual synchronized, localized or widely distributed neuronal electrical discharges.^[2]
• The underlying event in all types of seizures is the paroxysmal depolarization shift (PDS) which also causes the EEG changes.^[3]
• In a normal circumstance we have a refractory period after every action potential, but in PDS, the absence of refractory period causes a prolonged membrane depolarization.^[4]
• The likelihood of PDS happening depends on so many factors such as intrinsic neuronal characteristic (channelopathies) and extrinsic characteristics (excess excitatory or inadequate inhibitory neurotransmitters).
• In order to cause a seizure, so many PDSs most happen in the same time.^[5]
• Any alternation in a synaptic characteristics can prone a person to epilepsy. They include:
  • Amount of neurotransmitters
  • Function of inhibitory neurons
  • Function of excitatory neurons
  • Synaptic structure
  • Ion channels involved in neurotransmitter release and conduction of action potential.^[6]
• The underlying pathophysiology of focal epilepsy is different than generalized epilepsy.
  • Focal epilepsy:
    • In these kind of seizures, epileptiform activity starts in a specific area of brain. It can further spread and cause secondary generalized seizure.
  • Generalized epilepsy:
    • These seizures occur in both cerebral hemispheres simultaneously or spread so fast from one to another that in EEG, we can see bilateral epileptiform activity from the start.^[7]

Genetics[edit | edit source]

• There are many genes involved in ion channels and neurotransmitter receptors. The polymorphism of these genes determine a person’s susceptibility for developing epilepsy after an offending injury.^[8]

• Mutations in several genes have been linked to some types of epilepsy. Several genes that code for protein subunits of voltage-gated and ligand-gated ion channels have been associated with forms of generalized epilepsy and infantile seizure syndromes.^[9]
• there are some forms of Mendelian syndromes which are the result of mutation in SCN1A gene (Dravet syndrome) or GABR1 gene (autosomal dominant nocturnal frontal lobe epilepsy, juvenile myoclonic epilepsy).^[8]

Gross Pathology[edit | edit source]

• On gross pathology, slight opacity and thickening of the meninges, signs of meningitis, vascular disturbances, ecchymoses on the surface of various organs and fatty changes in the heart and striated muscles can be seen in epilepsy.^[10]

Microscopic Pathology[edit | edit source]

• On microscopic pathology histopathological analysis:
  • In the hippocampus of patients with temporal lobe epilepsy there is evidence of cell loss mainly in CA1 and CA4 sectors, CA1 neuron loss and gliosis and CA4 neuronal cell loss and gliosis.
  • In dentate gyrus there is evidence of Substantial granule cell loss and Cell dispersion.^[11]

References[edit | edit source]

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